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LitCovid-PubTator

{"project":"LitCovid-PubTator","denotations":[{"id":"621","span":{"begin":171,"end":180},"obj":"Chemical"},{"id":"624","span":{"begin":788,"end":797},"obj":"Chemical"},{"id":"625","span":{"begin":1186,"end":1195},"obj":"Chemical"},{"id":"630","span":{"begin":1446,"end":1449},"obj":"Gene"},{"id":"631","span":{"begin":1588,"end":1591},"obj":"Gene"},{"id":"632","span":{"begin":1900,"end":1904},"obj":"Gene"},{"id":"633","span":{"begin":1311,"end":1320},"obj":"Chemical"},{"id":"635","span":{"begin":1987,"end":1991},"obj":"Gene"}],"attributes":[{"id":"A621","pred":"tao:has_database_id","subj":"621","obj":"MESH:D004220"},{"id":"A624","pred":"tao:has_database_id","subj":"624","obj":"MESH:D004220"},{"id":"A625","pred":"tao:has_database_id","subj":"625","obj":"MESH:D004220"},{"id":"A630","pred":"tao:has_database_id","subj":"630","obj":"Gene:51430"},{"id":"A631","pred":"tao:has_database_id","subj":"631","obj":"Gene:51430"},{"id":"A632","pred":"tao:has_database_id","subj":"632","obj":"Gene:2213"},{"id":"A633","pred":"tao:has_database_id","subj":"633","obj":"MESH:D004220"},{"id":"A635","pred":"tao:has_database_id","subj":"635","obj":"Gene:3502"}],"namespaces":[{"prefix":"Tax","uri":"https://www.ncbi.nlm.nih.gov/taxonomy/"},{"prefix":"MESH","uri":"https://id.nlm.nih.gov/mesh/"},{"prefix":"Gene","uri":"https://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"CVCL","uri":"https://web.expasy.org/cellosaurus/CVCL_"}],"text":"Unique features of the IgG2 and IgG4 subclasses\nIn IgG1, the stable interaction of the two heavy chains results from the combined effects of stable covalent inter H‐chain disulfide bonds and strong noncovalent interaction of the two CH3 domains (Table 3). In stark contrast, in IgG2 and IgG4 the interaction of the CH3 domains of each H‐chain is weak. Residues 392, 397 and 409 (Eu numbering) profoundly affect the stability of these interactions. The difference at position 409 (R409 in IgG4 and K409 in IgG1) confers a 100‐fold decrease in stability of the interface between the two CH3 domains of IgG4 compared with that of IgG1 (Table 3).69\nFurthermore, the core hinge of IgG4 differs from IgG1 at position 228 (P228 in IgG1 and S228 in IgG4), resulting in unstable inter‐heavy‐chain disulfide bonds. This, together with the destabilizing amino acids in the CH3, confers the unique property of half‐antibody (Fab arm) exchange between different IgG4 antibodies,69 thereby creating monovalent, bispecific IgG4 antibodies in vivo.69, 70 The similarly unstable interactions between the CH3 domains in IgG2 are conferred by the interface residue M397; however, the stable inter‐H‐chain disulfide bonds of the core and upper hinge prevent half‐molecule exchange (Table 3).69\nIn addition, IgG2 uniquely has three disulfide bond conformers (Table 3). The distinct conformers are formed when (1) each light chain is attached to the Cys131 residue of CH1 in the heavy chain (IgG2‐A conformer), (2) both light chains attach to the upper hinge (IgG2‐B) or (3) one light chain is attached to the CH1 Cys131 and one to the upper hinge of the other heavy chain (IgG2‐AB).71 This results in distinct positioning of the Fabs relative to the Fc portions in the different conformers, which has implications for the interaction with antigen and the capacity of IgG2 to cross‐link target molecules in the absence of FcγR binding, for example, in an agonistic mAb setting.72\nIt should also be noted that IgG3 has not been used in therapeutic mAbs despite its unique biology. The main impediment to its use are its physicochemical properties such as susceptibility to proteolysis and propensity to aggregate that present challenges to industry‐scale production and stability but protein engineering is attempting to overcome these hurdles.73"}

LitCovid-PD-FMA-UBERON

{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T336","span":{"begin":843,"end":854},"obj":"Body_part"},{"id":"T337","span":{"begin":903,"end":911},"obj":"Body_part"},{"id":"T338","span":{"begin":917,"end":920},"obj":"Body_part"},{"id":"T339","span":{"begin":2261,"end":2268},"obj":"Body_part"}],"attributes":[{"id":"A336","pred":"fma_id","subj":"T336","obj":"http://purl.org/sig/ont/fma/fma82739"},{"id":"A337","pred":"fma_id","subj":"T337","obj":"http://purl.org/sig/ont/fma/fma62871"},{"id":"A338","pred":"fma_id","subj":"T338","obj":"http://purl.org/sig/ont/fma/fma24890"},{"id":"A339","pred":"fma_id","subj":"T339","obj":"http://purl.org/sig/ont/fma/fma67257"}],"text":"Unique features of the IgG2 and IgG4 subclasses\nIn IgG1, the stable interaction of the two heavy chains results from the combined effects of stable covalent inter H‐chain disulfide bonds and strong noncovalent interaction of the two CH3 domains (Table 3). In stark contrast, in IgG2 and IgG4 the interaction of the CH3 domains of each H‐chain is weak. Residues 392, 397 and 409 (Eu numbering) profoundly affect the stability of these interactions. The difference at position 409 (R409 in IgG4 and K409 in IgG1) confers a 100‐fold decrease in stability of the interface between the two CH3 domains of IgG4 compared with that of IgG1 (Table 3).69\nFurthermore, the core hinge of IgG4 differs from IgG1 at position 228 (P228 in IgG1 and S228 in IgG4), resulting in unstable inter‐heavy‐chain disulfide bonds. This, together with the destabilizing amino acids in the CH3, confers the unique property of half‐antibody (Fab arm) exchange between different IgG4 antibodies,69 thereby creating monovalent, bispecific IgG4 antibodies in vivo.69, 70 The similarly unstable interactions between the CH3 domains in IgG2 are conferred by the interface residue M397; however, the stable inter‐H‐chain disulfide bonds of the core and upper hinge prevent half‐molecule exchange (Table 3).69\nIn addition, IgG2 uniquely has three disulfide bond conformers (Table 3). The distinct conformers are formed when (1) each light chain is attached to the Cys131 residue of CH1 in the heavy chain (IgG2‐A conformer), (2) both light chains attach to the upper hinge (IgG2‐B) or (3) one light chain is attached to the CH1 Cys131 and one to the upper hinge of the other heavy chain (IgG2‐AB).71 This results in distinct positioning of the Fabs relative to the Fc portions in the different conformers, which has implications for the interaction with antigen and the capacity of IgG2 to cross‐link target molecules in the absence of FcγR binding, for example, in an agonistic mAb setting.72\nIt should also be noted that IgG3 has not been used in therapeutic mAbs despite its unique biology. The main impediment to its use are its physicochemical properties such as susceptibility to proteolysis and propensity to aggregate that present challenges to industry‐scale production and stability but protein engineering is attempting to overcome these hurdles.73"}

LitCovid-PD-UBERON

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T19","span":{"begin":917,"end":920},"obj":"Body_part"},{"id":"T20","span":{"begin":2226,"end":2231},"obj":"Body_part"}],"attributes":[{"id":"A19","pred":"uberon_id","subj":"T19","obj":"http://purl.obolibrary.org/obo/UBERON_0001460"},{"id":"A20","pred":"uberon_id","subj":"T20","obj":"http://purl.obolibrary.org/obo/UBERON_0002542"}],"text":"Unique features of the IgG2 and IgG4 subclasses\nIn IgG1, the stable interaction of the two heavy chains results from the combined effects of stable covalent inter H‐chain disulfide bonds and strong noncovalent interaction of the two CH3 domains (Table 3). In stark contrast, in IgG2 and IgG4 the interaction of the CH3 domains of each H‐chain is weak. Residues 392, 397 and 409 (Eu numbering) profoundly affect the stability of these interactions. The difference at position 409 (R409 in IgG4 and K409 in IgG1) confers a 100‐fold decrease in stability of the interface between the two CH3 domains of IgG4 compared with that of IgG1 (Table 3).69\nFurthermore, the core hinge of IgG4 differs from IgG1 at position 228 (P228 in IgG1 and S228 in IgG4), resulting in unstable inter‐heavy‐chain disulfide bonds. This, together with the destabilizing amino acids in the CH3, confers the unique property of half‐antibody (Fab arm) exchange between different IgG4 antibodies,69 thereby creating monovalent, bispecific IgG4 antibodies in vivo.69, 70 The similarly unstable interactions between the CH3 domains in IgG2 are conferred by the interface residue M397; however, the stable inter‐H‐chain disulfide bonds of the core and upper hinge prevent half‐molecule exchange (Table 3).69\nIn addition, IgG2 uniquely has three disulfide bond conformers (Table 3). The distinct conformers are formed when (1) each light chain is attached to the Cys131 residue of CH1 in the heavy chain (IgG2‐A conformer), (2) both light chains attach to the upper hinge (IgG2‐B) or (3) one light chain is attached to the CH1 Cys131 and one to the upper hinge of the other heavy chain (IgG2‐AB).71 This results in distinct positioning of the Fabs relative to the Fc portions in the different conformers, which has implications for the interaction with antigen and the capacity of IgG2 to cross‐link target molecules in the absence of FcγR binding, for example, in an agonistic mAb setting.72\nIt should also be noted that IgG3 has not been used in therapeutic mAbs despite its unique biology. The main impediment to its use are its physicochemical properties such as susceptibility to proteolysis and propensity to aggregate that present challenges to industry‐scale production and stability but protein engineering is attempting to overcome these hurdles.73"}

LitCovid-PD-CLO

{"project":"LitCovid-PD-CLO","denotations":[{"id":"T679","span":{"begin":519,"end":520},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T680","span":{"begin":917,"end":920},"obj":"http://www.ebi.ac.uk/efo/EFO_0001410"},{"id":"T681","span":{"begin":1301,"end":1304},"obj":"http://purl.obolibrary.org/obo/CLO_0051582"},{"id":"T682","span":{"begin":1446,"end":1449},"obj":"http://purl.obolibrary.org/obo/CLO_0002408"},{"id":"T683","span":{"begin":1475,"end":1476},"obj":"http://purl.obolibrary.org/obo/CLO_0001020"},{"id":"T684","span":{"begin":1543,"end":1544},"obj":"http://purl.obolibrary.org/obo/CLO_0001021"},{"id":"T685","span":{"begin":1588,"end":1591},"obj":"http://purl.obolibrary.org/obo/CLO_0002408"},{"id":"T686","span":{"begin":1661,"end":1663},"obj":"http://purl.obolibrary.org/obo/CLO_0054055"},{"id":"T687","span":{"begin":1729,"end":1731},"obj":"http://purl.obolibrary.org/obo/CLO_0052676"},{"id":"T688","span":{"begin":1776,"end":1779},"obj":"http://purl.obolibrary.org/obo/CLO_0051582"},{"id":"T689","span":{"begin":1900,"end":1902},"obj":"http://purl.obolibrary.org/obo/CLO_0052676"},{"id":"T690","span":{"begin":1992,"end":1995},"obj":"http://purl.obolibrary.org/obo/CLO_0051582"}],"text":"Unique features of the IgG2 and IgG4 subclasses\nIn IgG1, the stable interaction of the two heavy chains results from the combined effects of stable covalent inter H‐chain disulfide bonds and strong noncovalent interaction of the two CH3 domains (Table 3). In stark contrast, in IgG2 and IgG4 the interaction of the CH3 domains of each H‐chain is weak. Residues 392, 397 and 409 (Eu numbering) profoundly affect the stability of these interactions. The difference at position 409 (R409 in IgG4 and K409 in IgG1) confers a 100‐fold decrease in stability of the interface between the two CH3 domains of IgG4 compared with that of IgG1 (Table 3).69\nFurthermore, the core hinge of IgG4 differs from IgG1 at position 228 (P228 in IgG1 and S228 in IgG4), resulting in unstable inter‐heavy‐chain disulfide bonds. This, together with the destabilizing amino acids in the CH3, confers the unique property of half‐antibody (Fab arm) exchange between different IgG4 antibodies,69 thereby creating monovalent, bispecific IgG4 antibodies in vivo.69, 70 The similarly unstable interactions between the CH3 domains in IgG2 are conferred by the interface residue M397; however, the stable inter‐H‐chain disulfide bonds of the core and upper hinge prevent half‐molecule exchange (Table 3).69\nIn addition, IgG2 uniquely has three disulfide bond conformers (Table 3). The distinct conformers are formed when (1) each light chain is attached to the Cys131 residue of CH1 in the heavy chain (IgG2‐A conformer), (2) both light chains attach to the upper hinge (IgG2‐B) or (3) one light chain is attached to the CH1 Cys131 and one to the upper hinge of the other heavy chain (IgG2‐AB).71 This results in distinct positioning of the Fabs relative to the Fc portions in the different conformers, which has implications for the interaction with antigen and the capacity of IgG2 to cross‐link target molecules in the absence of FcγR binding, for example, in an agonistic mAb setting.72\nIt should also be noted that IgG3 has not been used in therapeutic mAbs despite its unique biology. The main impediment to its use are its physicochemical properties such as susceptibility to proteolysis and propensity to aggregate that present challenges to industry‐scale production and stability but protein engineering is attempting to overcome these hurdles.73"}

LitCovid-PD-CHEBI

LitCovid-sample-PD-IDO

{"project":"LitCovid-sample-PD-IDO","denotations":[{"id":"T197","span":{"begin":2132,"end":2146},"obj":"http://purl.obolibrary.org/obo/IDO_0000467"},{"id":"T198","span":{"begin":2232,"end":2242},"obj":"http://purl.obolibrary.org/obo/IDO_0000607"}],"text":"Unique features of the IgG2 and IgG4 subclasses\nIn IgG1, the stable interaction of the two heavy chains results from the combined effects of stable covalent inter H‐chain disulfide bonds and strong noncovalent interaction of the two CH3 domains (Table 3). In stark contrast, in IgG2 and IgG4 the interaction of the CH3 domains of each H‐chain is weak. Residues 392, 397 and 409 (Eu numbering) profoundly affect the stability of these interactions. The difference at position 409 (R409 in IgG4 and K409 in IgG1) confers a 100‐fold decrease in stability of the interface between the two CH3 domains of IgG4 compared with that of IgG1 (Table 3).69\nFurthermore, the core hinge of IgG4 differs from IgG1 at position 228 (P228 in IgG1 and S228 in IgG4), resulting in unstable inter‐heavy‐chain disulfide bonds. This, together with the destabilizing amino acids in the CH3, confers the unique property of half‐antibody (Fab arm) exchange between different IgG4 antibodies,69 thereby creating monovalent, bispecific IgG4 antibodies in vivo.69, 70 The similarly unstable interactions between the CH3 domains in IgG2 are conferred by the interface residue M397; however, the stable inter‐H‐chain disulfide bonds of the core and upper hinge prevent half‐molecule exchange (Table 3).69\nIn addition, IgG2 uniquely has three disulfide bond conformers (Table 3). The distinct conformers are formed when (1) each light chain is attached to the Cys131 residue of CH1 in the heavy chain (IgG2‐A conformer), (2) both light chains attach to the upper hinge (IgG2‐B) or (3) one light chain is attached to the CH1 Cys131 and one to the upper hinge of the other heavy chain (IgG2‐AB).71 This results in distinct positioning of the Fabs relative to the Fc portions in the different conformers, which has implications for the interaction with antigen and the capacity of IgG2 to cross‐link target molecules in the absence of FcγR binding, for example, in an agonistic mAb setting.72\nIt should also be noted that IgG3 has not been used in therapeutic mAbs despite its unique biology. The main impediment to its use are its physicochemical properties such as susceptibility to proteolysis and propensity to aggregate that present challenges to industry‐scale production and stability but protein engineering is attempting to overcome these hurdles.73"}

LitCovid-sample-CHEBI

{"project":"LitCovid-sample-CHEBI","denotations":[{"id":"T40","span":{"begin":171,"end":180},"obj":"Chemical"},{"id":"T41","span":{"begin":788,"end":797},"obj":"Chemical"},{"id":"T42","span":{"begin":843,"end":854},"obj":"Chemical"},{"id":"T43","span":{"begin":1186,"end":1195},"obj":"Chemical"},{"id":"T44","span":{"begin":1311,"end":1320},"obj":"Chemical"},{"id":"T45","span":{"begin":2261,"end":2268},"obj":"Chemical"}],"attributes":[{"id":"A40","pred":"chebi_id","subj":"T40","obj":"http://purl.obolibrary.org/obo/CHEBI_48343"},{"id":"A41","pred":"chebi_id","subj":"T41","obj":"http://purl.obolibrary.org/obo/CHEBI_48343"},{"id":"A42","pred":"chebi_id","subj":"T42","obj":"http://purl.obolibrary.org/obo/CHEBI_33709"},{"id":"A43","pred":"chebi_id","subj":"T43","obj":"http://purl.obolibrary.org/obo/CHEBI_48343"},{"id":"A44","pred":"chebi_id","subj":"T44","obj":"http://purl.obolibrary.org/obo/CHEBI_48343"},{"id":"A45","pred":"chebi_id","subj":"T45","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"}],"text":"Unique features of the IgG2 and IgG4 subclasses\nIn IgG1, the stable interaction of the two heavy chains results from the combined effects of stable covalent inter H‐chain disulfide bonds and strong noncovalent interaction of the two CH3 domains (Table 3). In stark contrast, in IgG2 and IgG4 the interaction of the CH3 domains of each H‐chain is weak. Residues 392, 397 and 409 (Eu numbering) profoundly affect the stability of these interactions. The difference at position 409 (R409 in IgG4 and K409 in IgG1) confers a 100‐fold decrease in stability of the interface between the two CH3 domains of IgG4 compared with that of IgG1 (Table 3).69\nFurthermore, the core hinge of IgG4 differs from IgG1 at position 228 (P228 in IgG1 and S228 in IgG4), resulting in unstable inter‐heavy‐chain disulfide bonds. This, together with the destabilizing amino acids in the CH3, confers the unique property of half‐antibody (Fab arm) exchange between different IgG4 antibodies,69 thereby creating monovalent, bispecific IgG4 antibodies in vivo.69, 70 The similarly unstable interactions between the CH3 domains in IgG2 are conferred by the interface residue M397; however, the stable inter‐H‐chain disulfide bonds of the core and upper hinge prevent half‐molecule exchange (Table 3).69\nIn addition, IgG2 uniquely has three disulfide bond conformers (Table 3). The distinct conformers are formed when (1) each light chain is attached to the Cys131 residue of CH1 in the heavy chain (IgG2‐A conformer), (2) both light chains attach to the upper hinge (IgG2‐B) or (3) one light chain is attached to the CH1 Cys131 and one to the upper hinge of the other heavy chain (IgG2‐AB).71 This results in distinct positioning of the Fabs relative to the Fc portions in the different conformers, which has implications for the interaction with antigen and the capacity of IgG2 to cross‐link target molecules in the absence of FcγR binding, for example, in an agonistic mAb setting.72\nIt should also be noted that IgG3 has not been used in therapeutic mAbs despite its unique biology. The main impediment to its use are its physicochemical properties such as susceptibility to proteolysis and propensity to aggregate that present challenges to industry‐scale production and stability but protein engineering is attempting to overcome these hurdles.73"}

LitCovid-sample-Pubtator

{"project":"LitCovid-sample-Pubtator","denotations":[{"id":"621","span":{"begin":171,"end":180},"obj":"Chemical"},{"id":"624","span":{"begin":788,"end":797},"obj":"Chemical"},{"id":"625","span":{"begin":1186,"end":1195},"obj":"Chemical"},{"id":"630","span":{"begin":1446,"end":1449},"obj":"Gene"},{"id":"631","span":{"begin":1588,"end":1591},"obj":"Gene"},{"id":"632","span":{"begin":1900,"end":1904},"obj":"Gene"},{"id":"633","span":{"begin":1311,"end":1320},"obj":"Chemical"},{"id":"635","span":{"begin":1987,"end":1991},"obj":"Gene"}],"attributes":[{"id":"A631","pred":"pubann:denotes","subj":"631","obj":"Gene:51430"},{"id":"A635","pred":"pubann:denotes","subj":"635","obj":"Gene:3502"},{"id":"A621","pred":"pubann:denotes","subj":"621","obj":"MESH:D004220"},{"id":"A633","pred":"pubann:denotes","subj":"633","obj":"MESH:D004220"},{"id":"A624","pred":"pubann:denotes","subj":"624","obj":"MESH:D004220"},{"id":"A632","pred":"pubann:denotes","subj":"632","obj":"Gene:2213"},{"id":"A625","pred":"pubann:denotes","subj":"625","obj":"MESH:D004220"},{"id":"A630","pred":"pubann:denotes","subj":"630","obj":"Gene:51430"}],"text":"Unique features of the IgG2 and IgG4 subclasses\nIn IgG1, the stable interaction of the two heavy chains results from the combined effects of stable covalent inter H‐chain disulfide bonds and strong noncovalent interaction of the two CH3 domains (Table 3). In stark contrast, in IgG2 and IgG4 the interaction of the CH3 domains of each H‐chain is weak. Residues 392, 397 and 409 (Eu numbering) profoundly affect the stability of these interactions. The difference at position 409 (R409 in IgG4 and K409 in IgG1) confers a 100‐fold decrease in stability of the interface between the two CH3 domains of IgG4 compared with that of IgG1 (Table 3).69\nFurthermore, the core hinge of IgG4 differs from IgG1 at position 228 (P228 in IgG1 and S228 in IgG4), resulting in unstable inter‐heavy‐chain disulfide bonds. This, together with the destabilizing amino acids in the CH3, confers the unique property of half‐antibody (Fab arm) exchange between different IgG4 antibodies,69 thereby creating monovalent, bispecific IgG4 antibodies in vivo.69, 70 The similarly unstable interactions between the CH3 domains in IgG2 are conferred by the interface residue M397; however, the stable inter‐H‐chain disulfide bonds of the core and upper hinge prevent half‐molecule exchange (Table 3).69\nIn addition, IgG2 uniquely has three disulfide bond conformers (Table 3). The distinct conformers are formed when (1) each light chain is attached to the Cys131 residue of CH1 in the heavy chain (IgG2‐A conformer), (2) both light chains attach to the upper hinge (IgG2‐B) or (3) one light chain is attached to the CH1 Cys131 and one to the upper hinge of the other heavy chain (IgG2‐AB).71 This results in distinct positioning of the Fabs relative to the Fc portions in the different conformers, which has implications for the interaction with antigen and the capacity of IgG2 to cross‐link target molecules in the absence of FcγR binding, for example, in an agonistic mAb setting.72\nIt should also be noted that IgG3 has not been used in therapeutic mAbs despite its unique biology. The main impediment to its use are its physicochemical properties such as susceptibility to proteolysis and propensity to aggregate that present challenges to industry‐scale production and stability but protein engineering is attempting to overcome these hurdles.73"}

LitCovid-sample-sentences

{"project":"LitCovid-sample-sentences","denotations":[{"id":"T203","span":{"begin":0,"end":47},"obj":"Sentence"},{"id":"T204","span":{"begin":48,"end":255},"obj":"Sentence"},{"id":"T205","span":{"begin":256,"end":351},"obj":"Sentence"},{"id":"T206","span":{"begin":352,"end":447},"obj":"Sentence"},{"id":"T207","span":{"begin":448,"end":644},"obj":"Sentence"},{"id":"T208","span":{"begin":645,"end":804},"obj":"Sentence"},{"id":"T209","span":{"begin":805,"end":1273},"obj":"Sentence"},{"id":"T210","span":{"begin":1274,"end":1347},"obj":"Sentence"},{"id":"T211","span":{"begin":1348,"end":1957},"obj":"Sentence"},{"id":"T212","span":{"begin":1958,"end":2057},"obj":"Sentence"},{"id":"T213","span":{"begin":2058,"end":2323},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Unique features of the IgG2 and IgG4 subclasses\nIn IgG1, the stable interaction of the two heavy chains results from the combined effects of stable covalent inter H‐chain disulfide bonds and strong noncovalent interaction of the two CH3 domains (Table 3). In stark contrast, in IgG2 and IgG4 the interaction of the CH3 domains of each H‐chain is weak. Residues 392, 397 and 409 (Eu numbering) profoundly affect the stability of these interactions. The difference at position 409 (R409 in IgG4 and K409 in IgG1) confers a 100‐fold decrease in stability of the interface between the two CH3 domains of IgG4 compared with that of IgG1 (Table 3).69\nFurthermore, the core hinge of IgG4 differs from IgG1 at position 228 (P228 in IgG1 and S228 in IgG4), resulting in unstable inter‐heavy‐chain disulfide bonds. This, together with the destabilizing amino acids in the CH3, confers the unique property of half‐antibody (Fab arm) exchange between different IgG4 antibodies,69 thereby creating monovalent, bispecific IgG4 antibodies in vivo.69, 70 The similarly unstable interactions between the CH3 domains in IgG2 are conferred by the interface residue M397; however, the stable inter‐H‐chain disulfide bonds of the core and upper hinge prevent half‐molecule exchange (Table 3).69\nIn addition, IgG2 uniquely has three disulfide bond conformers (Table 3). The distinct conformers are formed when (1) each light chain is attached to the Cys131 residue of CH1 in the heavy chain (IgG2‐A conformer), (2) both light chains attach to the upper hinge (IgG2‐B) or (3) one light chain is attached to the CH1 Cys131 and one to the upper hinge of the other heavy chain (IgG2‐AB).71 This results in distinct positioning of the Fabs relative to the Fc portions in the different conformers, which has implications for the interaction with antigen and the capacity of IgG2 to cross‐link target molecules in the absence of FcγR binding, for example, in an agonistic mAb setting.72\nIt should also be noted that IgG3 has not been used in therapeutic mAbs despite its unique biology. The main impediment to its use are its physicochemical properties such as susceptibility to proteolysis and propensity to aggregate that present challenges to industry‐scale production and stability but protein engineering is attempting to overcome these hurdles.73"}

LitCovid-sample-PD-UBERON

{"project":"LitCovid-sample-PD-UBERON","denotations":[{"id":"T19","span":{"begin":917,"end":920},"obj":"Body_part"},{"id":"T20","span":{"begin":2226,"end":2231},"obj":"Body_part"}],"attributes":[{"id":"A19","pred":"uberon_id","subj":"T19","obj":"http://purl.obolibrary.org/obo/UBERON_0001460"},{"id":"A20","pred":"uberon_id","subj":"T20","obj":"http://purl.obolibrary.org/obo/UBERON_0002542"}],"text":"Unique features of the IgG2 and IgG4 subclasses\nIn IgG1, the stable interaction of the two heavy chains results from the combined effects of stable covalent inter H‐chain disulfide bonds and strong noncovalent interaction of the two CH3 domains (Table 3). In stark contrast, in IgG2 and IgG4 the interaction of the CH3 domains of each H‐chain is weak. Residues 392, 397 and 409 (Eu numbering) profoundly affect the stability of these interactions. The difference at position 409 (R409 in IgG4 and K409 in IgG1) confers a 100‐fold decrease in stability of the interface between the two CH3 domains of IgG4 compared with that of IgG1 (Table 3).69\nFurthermore, the core hinge of IgG4 differs from IgG1 at position 228 (P228 in IgG1 and S228 in IgG4), resulting in unstable inter‐heavy‐chain disulfide bonds. This, together with the destabilizing amino acids in the CH3, confers the unique property of half‐antibody (Fab arm) exchange between different IgG4 antibodies,69 thereby creating monovalent, bispecific IgG4 antibodies in vivo.69, 70 The similarly unstable interactions between the CH3 domains in IgG2 are conferred by the interface residue M397; however, the stable inter‐H‐chain disulfide bonds of the core and upper hinge prevent half‐molecule exchange (Table 3).69\nIn addition, IgG2 uniquely has three disulfide bond conformers (Table 3). The distinct conformers are formed when (1) each light chain is attached to the Cys131 residue of CH1 in the heavy chain (IgG2‐A conformer), (2) both light chains attach to the upper hinge (IgG2‐B) or (3) one light chain is attached to the CH1 Cys131 and one to the upper hinge of the other heavy chain (IgG2‐AB).71 This results in distinct positioning of the Fabs relative to the Fc portions in the different conformers, which has implications for the interaction with antigen and the capacity of IgG2 to cross‐link target molecules in the absence of FcγR binding, for example, in an agonistic mAb setting.72\nIt should also be noted that IgG3 has not been used in therapeutic mAbs despite its unique biology. The main impediment to its use are its physicochemical properties such as susceptibility to proteolysis and propensity to aggregate that present challenges to industry‐scale production and stability but protein engineering is attempting to overcome these hurdles.73"}

LitCovid-sample-PD-FMA

{"project":"LitCovid-sample-PD-FMA","denotations":[{"id":"T335","span":{"begin":843,"end":854},"obj":"Body_part"},{"id":"T336","span":{"begin":903,"end":911},"obj":"Body_part"},{"id":"T337","span":{"begin":917,"end":920},"obj":"Body_part"},{"id":"T338","span":{"begin":2261,"end":2268},"obj":"Body_part"}],"attributes":[{"id":"A335","pred":"fma_id","subj":"T335","obj":"http://purl.org/sig/ont/fma/fma82739"},{"id":"A336","pred":"fma_id","subj":"T336","obj":"http://purl.org/sig/ont/fma/fma62871"},{"id":"A337","pred":"fma_id","subj":"T337","obj":"http://purl.org/sig/ont/fma/fma24890"},{"id":"A338","pred":"fma_id","subj":"T338","obj":"http://purl.org/sig/ont/fma/fma67257"}],"text":"Unique features of the IgG2 and IgG4 subclasses\nIn IgG1, the stable interaction of the two heavy chains results from the combined effects of stable covalent inter H‐chain disulfide bonds and strong noncovalent interaction of the two CH3 domains (Table 3). In stark contrast, in IgG2 and IgG4 the interaction of the CH3 domains of each H‐chain is weak. Residues 392, 397 and 409 (Eu numbering) profoundly affect the stability of these interactions. The difference at position 409 (R409 in IgG4 and K409 in IgG1) confers a 100‐fold decrease in stability of the interface between the two CH3 domains of IgG4 compared with that of IgG1 (Table 3).69\nFurthermore, the core hinge of IgG4 differs from IgG1 at position 228 (P228 in IgG1 and S228 in IgG4), resulting in unstable inter‐heavy‐chain disulfide bonds. This, together with the destabilizing amino acids in the CH3, confers the unique property of half‐antibody (Fab arm) exchange between different IgG4 antibodies,69 thereby creating monovalent, bispecific IgG4 antibodies in vivo.69, 70 The similarly unstable interactions between the CH3 domains in IgG2 are conferred by the interface residue M397; however, the stable inter‐H‐chain disulfide bonds of the core and upper hinge prevent half‐molecule exchange (Table 3).69\nIn addition, IgG2 uniquely has three disulfide bond conformers (Table 3). The distinct conformers are formed when (1) each light chain is attached to the Cys131 residue of CH1 in the heavy chain (IgG2‐A conformer), (2) both light chains attach to the upper hinge (IgG2‐B) or (3) one light chain is attached to the CH1 Cys131 and one to the upper hinge of the other heavy chain (IgG2‐AB).71 This results in distinct positioning of the Fabs relative to the Fc portions in the different conformers, which has implications for the interaction with antigen and the capacity of IgG2 to cross‐link target molecules in the absence of FcγR binding, for example, in an agonistic mAb setting.72\nIt should also be noted that IgG3 has not been used in therapeutic mAbs despite its unique biology. The main impediment to its use are its physicochemical properties such as susceptibility to proteolysis and propensity to aggregate that present challenges to industry‐scale production and stability but protein engineering is attempting to overcome these hurdles.73"}

LitCovid-sample-PD-GO-BP-0

{"project":"LitCovid-sample-PD-GO-BP-0","denotations":[{"id":"T91","span":{"begin":922,"end":930},"obj":"http://purl.obolibrary.org/obo/GO_0015297"},{"id":"T92","span":{"begin":1252,"end":1260},"obj":"http://purl.obolibrary.org/obo/GO_0015297"},{"id":"T93","span":{"begin":2150,"end":2161},"obj":"http://purl.obolibrary.org/obo/GO_0006508"}],"text":"Unique features of the IgG2 and IgG4 subclasses\nIn IgG1, the stable interaction of the two heavy chains results from the combined effects of stable covalent inter H‐chain disulfide bonds and strong noncovalent interaction of the two CH3 domains (Table 3). In stark contrast, in IgG2 and IgG4 the interaction of the CH3 domains of each H‐chain is weak. Residues 392, 397 and 409 (Eu numbering) profoundly affect the stability of these interactions. The difference at position 409 (R409 in IgG4 and K409 in IgG1) confers a 100‐fold decrease in stability of the interface between the two CH3 domains of IgG4 compared with that of IgG1 (Table 3).69\nFurthermore, the core hinge of IgG4 differs from IgG1 at position 228 (P228 in IgG1 and S228 in IgG4), resulting in unstable inter‐heavy‐chain disulfide bonds. This, together with the destabilizing amino acids in the CH3, confers the unique property of half‐antibody (Fab arm) exchange between different IgG4 antibodies,69 thereby creating monovalent, bispecific IgG4 antibodies in vivo.69, 70 The similarly unstable interactions between the CH3 domains in IgG2 are conferred by the interface residue M397; however, the stable inter‐H‐chain disulfide bonds of the core and upper hinge prevent half‐molecule exchange (Table 3).69\nIn addition, IgG2 uniquely has three disulfide bond conformers (Table 3). The distinct conformers are formed when (1) each light chain is attached to the Cys131 residue of CH1 in the heavy chain (IgG2‐A conformer), (2) both light chains attach to the upper hinge (IgG2‐B) or (3) one light chain is attached to the CH1 Cys131 and one to the upper hinge of the other heavy chain (IgG2‐AB).71 This results in distinct positioning of the Fabs relative to the Fc portions in the different conformers, which has implications for the interaction with antigen and the capacity of IgG2 to cross‐link target molecules in the absence of FcγR binding, for example, in an agonistic mAb setting.72\nIt should also be noted that IgG3 has not been used in therapeutic mAbs despite its unique biology. The main impediment to its use are its physicochemical properties such as susceptibility to proteolysis and propensity to aggregate that present challenges to industry‐scale production and stability but protein engineering is attempting to overcome these hurdles.73"}

LitCovid-sample-GO-BP

{"project":"LitCovid-sample-GO-BP","denotations":[{"id":"T92","span":{"begin":922,"end":930},"obj":"http://purl.obolibrary.org/obo/GO_0015297"},{"id":"T93","span":{"begin":1252,"end":1260},"obj":"http://purl.obolibrary.org/obo/GO_0015297"},{"id":"T94","span":{"begin":2150,"end":2161},"obj":"http://purl.obolibrary.org/obo/GO_0006508"}],"text":"Unique features of the IgG2 and IgG4 subclasses\nIn IgG1, the stable interaction of the two heavy chains results from the combined effects of stable covalent inter H‐chain disulfide bonds and strong noncovalent interaction of the two CH3 domains (Table 3). In stark contrast, in IgG2 and IgG4 the interaction of the CH3 domains of each H‐chain is weak. Residues 392, 397 and 409 (Eu numbering) profoundly affect the stability of these interactions. The difference at position 409 (R409 in IgG4 and K409 in IgG1) confers a 100‐fold decrease in stability of the interface between the two CH3 domains of IgG4 compared with that of IgG1 (Table 3).69\nFurthermore, the core hinge of IgG4 differs from IgG1 at position 228 (P228 in IgG1 and S228 in IgG4), resulting in unstable inter‐heavy‐chain disulfide bonds. This, together with the destabilizing amino acids in the CH3, confers the unique property of half‐antibody (Fab arm) exchange between different IgG4 antibodies,69 thereby creating monovalent, bispecific IgG4 antibodies in vivo.69, 70 The similarly unstable interactions between the CH3 domains in IgG2 are conferred by the interface residue M397; however, the stable inter‐H‐chain disulfide bonds of the core and upper hinge prevent half‐molecule exchange (Table 3).69\nIn addition, IgG2 uniquely has three disulfide bond conformers (Table 3). The distinct conformers are formed when (1) each light chain is attached to the Cys131 residue of CH1 in the heavy chain (IgG2‐A conformer), (2) both light chains attach to the upper hinge (IgG2‐B) or (3) one light chain is attached to the CH1 Cys131 and one to the upper hinge of the other heavy chain (IgG2‐AB).71 This results in distinct positioning of the Fabs relative to the Fc portions in the different conformers, which has implications for the interaction with antigen and the capacity of IgG2 to cross‐link target molecules in the absence of FcγR binding, for example, in an agonistic mAb setting.72\nIt should also be noted that IgG3 has not been used in therapeutic mAbs despite its unique biology. The main impediment to its use are its physicochemical properties such as susceptibility to proteolysis and propensity to aggregate that present challenges to industry‐scale production and stability but protein engineering is attempting to overcome these hurdles.73"}

LitCovid-PD-GO-BP

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T92","span":{"begin":922,"end":930},"obj":"http://purl.obolibrary.org/obo/GO_0015297"},{"id":"T93","span":{"begin":1252,"end":1260},"obj":"http://purl.obolibrary.org/obo/GO_0015297"},{"id":"T94","span":{"begin":2150,"end":2161},"obj":"http://purl.obolibrary.org/obo/GO_0006508"}],"text":"Unique features of the IgG2 and IgG4 subclasses\nIn IgG1, the stable interaction of the two heavy chains results from the combined effects of stable covalent inter H‐chain disulfide bonds and strong noncovalent interaction of the two CH3 domains (Table 3). In stark contrast, in IgG2 and IgG4 the interaction of the CH3 domains of each H‐chain is weak. Residues 392, 397 and 409 (Eu numbering) profoundly affect the stability of these interactions. The difference at position 409 (R409 in IgG4 and K409 in IgG1) confers a 100‐fold decrease in stability of the interface between the two CH3 domains of IgG4 compared with that of IgG1 (Table 3).69\nFurthermore, the core hinge of IgG4 differs from IgG1 at position 228 (P228 in IgG1 and S228 in IgG4), resulting in unstable inter‐heavy‐chain disulfide bonds. This, together with the destabilizing amino acids in the CH3, confers the unique property of half‐antibody (Fab arm) exchange between different IgG4 antibodies,69 thereby creating monovalent, bispecific IgG4 antibodies in vivo.69, 70 The similarly unstable interactions between the CH3 domains in IgG2 are conferred by the interface residue M397; however, the stable inter‐H‐chain disulfide bonds of the core and upper hinge prevent half‐molecule exchange (Table 3).69\nIn addition, IgG2 uniquely has three disulfide bond conformers (Table 3). The distinct conformers are formed when (1) each light chain is attached to the Cys131 residue of CH1 in the heavy chain (IgG2‐A conformer), (2) both light chains attach to the upper hinge (IgG2‐B) or (3) one light chain is attached to the CH1 Cys131 and one to the upper hinge of the other heavy chain (IgG2‐AB).71 This results in distinct positioning of the Fabs relative to the Fc portions in the different conformers, which has implications for the interaction with antigen and the capacity of IgG2 to cross‐link target molecules in the absence of FcγR binding, for example, in an agonistic mAb setting.72\nIt should also be noted that IgG3 has not been used in therapeutic mAbs despite its unique biology. The main impediment to its use are its physicochemical properties such as susceptibility to proteolysis and propensity to aggregate that present challenges to industry‐scale production and stability but protein engineering is attempting to overcome these hurdles.73"}

LitCovid-sentences

{"project":"LitCovid-sentences","denotations":[{"id":"T203","span":{"begin":0,"end":47},"obj":"Sentence"},{"id":"T204","span":{"begin":48,"end":255},"obj":"Sentence"},{"id":"T205","span":{"begin":256,"end":351},"obj":"Sentence"},{"id":"T206","span":{"begin":352,"end":447},"obj":"Sentence"},{"id":"T207","span":{"begin":448,"end":644},"obj":"Sentence"},{"id":"T208","span":{"begin":645,"end":804},"obj":"Sentence"},{"id":"T209","span":{"begin":805,"end":1273},"obj":"Sentence"},{"id":"T210","span":{"begin":1274,"end":1347},"obj":"Sentence"},{"id":"T211","span":{"begin":1348,"end":1957},"obj":"Sentence"},{"id":"T212","span":{"begin":1958,"end":2057},"obj":"Sentence"},{"id":"T213","span":{"begin":2058,"end":2323},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Unique features of the IgG2 and IgG4 subclasses\nIn IgG1, the stable interaction of the two heavy chains results from the combined effects of stable covalent inter H‐chain disulfide bonds and strong noncovalent interaction of the two CH3 domains (Table 3). In stark contrast, in IgG2 and IgG4 the interaction of the CH3 domains of each H‐chain is weak. Residues 392, 397 and 409 (Eu numbering) profoundly affect the stability of these interactions. The difference at position 409 (R409 in IgG4 and K409 in IgG1) confers a 100‐fold decrease in stability of the interface between the two CH3 domains of IgG4 compared with that of IgG1 (Table 3).69\nFurthermore, the core hinge of IgG4 differs from IgG1 at position 228 (P228 in IgG1 and S228 in IgG4), resulting in unstable inter‐heavy‐chain disulfide bonds. This, together with the destabilizing amino acids in the CH3, confers the unique property of half‐antibody (Fab arm) exchange between different IgG4 antibodies,69 thereby creating monovalent, bispecific IgG4 antibodies in vivo.69, 70 The similarly unstable interactions between the CH3 domains in IgG2 are conferred by the interface residue M397; however, the stable inter‐H‐chain disulfide bonds of the core and upper hinge prevent half‐molecule exchange (Table 3).69\nIn addition, IgG2 uniquely has three disulfide bond conformers (Table 3). The distinct conformers are formed when (1) each light chain is attached to the Cys131 residue of CH1 in the heavy chain (IgG2‐A conformer), (2) both light chains attach to the upper hinge (IgG2‐B) or (3) one light chain is attached to the CH1 Cys131 and one to the upper hinge of the other heavy chain (IgG2‐AB).71 This results in distinct positioning of the Fabs relative to the Fc portions in the different conformers, which has implications for the interaction with antigen and the capacity of IgG2 to cross‐link target molecules in the absence of FcγR binding, for example, in an agonistic mAb setting.72\nIt should also be noted that IgG3 has not been used in therapeutic mAbs despite its unique biology. The main impediment to its use are its physicochemical properties such as susceptibility to proteolysis and propensity to aggregate that present challenges to industry‐scale production and stability but protein engineering is attempting to overcome these hurdles.73"}

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