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LitCovid-sample-MedDRA

LitCovid-sample-CHEBI

LitCovid-sample-PD-NCBITaxon

{"project":"LitCovid-sample-PD-NCBITaxon","denotations":[{"id":"T35","span":{"begin":1021,"end":1025},"obj":"Species"}],"attributes":[{"id":"A35","pred":"ncbi_taxonomy_id","subj":"T35","obj":"NCBItxid:4530"}],"namespaces":[{"prefix":"NCBItxid","uri":"http://purl.bioontology.org/ontology/NCBITAXON/"}],"text":"Structure of ACE2\nACE2 is a 40 kb gene and it is positioned on chromosome Xp22, differently from ACE gene that is located on chromosome 17. The 18 exons of ACE2 are remarkably similar to ACE exons. The ACE2 gene depicts a large polymorphism and several novel polymorphisms of ACE2, with specific geographical distribution, have been described and associated with susceptibility to hypertension and cardiovascular disease (Burrell et al., 2013; Patel et al., 2014; Pinheiro et al., 2019).\nThe ACE2 gene codifies for a typical zinc-metallopeptidase of 805 amino acids (120 kDa), with a unique catalytic domain. Despite the high resemblance of ACE and ACE2, considerable differences exist in their substrates and products. While ACE acts as dipeptidase, ACE2 removes only a single amino acid from its substrates. Therefore, ACE2 is not active in transforming angiotensin I to angiotensin II and in inactivating bradykinin; moreover, ACE2 is insensitive to ACE inhibitors, like lisinopril and captopril (Tipnis et al., 2000; Rice et al., 2004; Turner et al., 2004).\nThese differences depend on variances in the three-dimensional structure (3D) of the two enzymes. Comparative homology modeling and crystallography contributed to shed light on ACE2 3D structure (Figure 1). Prabakaran et al. (2004) clarified the major characteristic of ACE2, which is a deep channel on the summit of the protein, hosting the catalytic domain. Specific loops, like the long loop N210-Q221 that is exclusive of ACE2, α helices and a portion of β-sheet are located around the catalytic channel. The negative charge of the channel and the presence of distinct hydrophobic regions contribute to the specificity of the binding site (Prabakaran et al., 2004). The determination of the crystal structure of the extracellular domain to 2.2-3-A resolution from Towler et al. (2004) and the model from Guy et al. (2003) showed that the catalytic domain of ACE and ACE2 are very conserved and have similar mechanisms of action. The main difference stems from the smaller ACE2 pocket, thereby lodging only a single amino acid: the crucial substitution of the Gln281 in ACE binding pocket with Arg273 in ACE2 is likely to be responsible for the steric conflict (Guy et al., 2003; Towler et al., 2004). Another surprise of the ACE2 structure was its C-terminal domain, which—differently from ACE—revealed high homology with collectrin, a renal protein, which is involved in amino acids trafficking through the membrane (Yang et al., 2017).\nFIGURE 1 Crystal structure of ACE2. The peptidase domain (PD) is in green, whereas the collectrin homology domain is enclosed in the light cyan square. The active zinc ion is showed enclosed in a red circle, whereas the glycosylation moieties are showed as cyan cubes and denoted by dashed arrows. The structures have been drawn from PDB 1R42 (Towler et al., 2004) by Mol on the PDB website."}

LitCovid-sample-sentences

{"project":"LitCovid-sample-sentences","denotations":[{"id":"T54","span":{"begin":0,"end":17},"obj":"Sentence"},{"id":"T55","span":{"begin":18,"end":139},"obj":"Sentence"},{"id":"T56","span":{"begin":140,"end":197},"obj":"Sentence"},{"id":"T57","span":{"begin":198,"end":487},"obj":"Sentence"},{"id":"T58","span":{"begin":488,"end":608},"obj":"Sentence"},{"id":"T59","span":{"begin":609,"end":719},"obj":"Sentence"},{"id":"T60","span":{"begin":720,"end":809},"obj":"Sentence"},{"id":"T61","span":{"begin":810,"end":1061},"obj":"Sentence"},{"id":"T62","span":{"begin":1062,"end":1159},"obj":"Sentence"},{"id":"T63","span":{"begin":1160,"end":1268},"obj":"Sentence"},{"id":"T64","span":{"begin":1269,"end":1421},"obj":"Sentence"},{"id":"T65","span":{"begin":1422,"end":1570},"obj":"Sentence"},{"id":"T66","span":{"begin":1571,"end":1731},"obj":"Sentence"},{"id":"T67","span":{"begin":1732,"end":1994},"obj":"Sentence"},{"id":"T68","span":{"begin":1995,"end":2266},"obj":"Sentence"},{"id":"T69","span":{"begin":2267,"end":2503},"obj":"Sentence"},{"id":"T70","span":{"begin":2504,"end":2540},"obj":"Sentence"},{"id":"T71","span":{"begin":2541,"end":2656},"obj":"Sentence"},{"id":"T72","span":{"begin":2657,"end":2802},"obj":"Sentence"},{"id":"T73","span":{"begin":2803,"end":2896},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Structure of ACE2\nACE2 is a 40 kb gene and it is positioned on chromosome Xp22, differently from ACE gene that is located on chromosome 17. The 18 exons of ACE2 are remarkably similar to ACE exons. The ACE2 gene depicts a large polymorphism and several novel polymorphisms of ACE2, with specific geographical distribution, have been described and associated with susceptibility to hypertension and cardiovascular disease (Burrell et al., 2013; Patel et al., 2014; Pinheiro et al., 2019).\nThe ACE2 gene codifies for a typical zinc-metallopeptidase of 805 amino acids (120 kDa), with a unique catalytic domain. Despite the high resemblance of ACE and ACE2, considerable differences exist in their substrates and products. While ACE acts as dipeptidase, ACE2 removes only a single amino acid from its substrates. Therefore, ACE2 is not active in transforming angiotensin I to angiotensin II and in inactivating bradykinin; moreover, ACE2 is insensitive to ACE inhibitors, like lisinopril and captopril (Tipnis et al., 2000; Rice et al., 2004; Turner et al., 2004).\nThese differences depend on variances in the three-dimensional structure (3D) of the two enzymes. Comparative homology modeling and crystallography contributed to shed light on ACE2 3D structure (Figure 1). Prabakaran et al. (2004) clarified the major characteristic of ACE2, which is a deep channel on the summit of the protein, hosting the catalytic domain. Specific loops, like the long loop N210-Q221 that is exclusive of ACE2, α helices and a portion of β-sheet are located around the catalytic channel. The negative charge of the channel and the presence of distinct hydrophobic regions contribute to the specificity of the binding site (Prabakaran et al., 2004). The determination of the crystal structure of the extracellular domain to 2.2-3-A resolution from Towler et al. (2004) and the model from Guy et al. (2003) showed that the catalytic domain of ACE and ACE2 are very conserved and have similar mechanisms of action. The main difference stems from the smaller ACE2 pocket, thereby lodging only a single amino acid: the crucial substitution of the Gln281 in ACE binding pocket with Arg273 in ACE2 is likely to be responsible for the steric conflict (Guy et al., 2003; Towler et al., 2004). Another surprise of the ACE2 structure was its C-terminal domain, which—differently from ACE—revealed high homology with collectrin, a renal protein, which is involved in amino acids trafficking through the membrane (Yang et al., 2017).\nFIGURE 1 Crystal structure of ACE2. The peptidase domain (PD) is in green, whereas the collectrin homology domain is enclosed in the light cyan square. The active zinc ion is showed enclosed in a red circle, whereas the glycosylation moieties are showed as cyan cubes and denoted by dashed arrows. The structures have been drawn from PDB 1R42 (Towler et al., 2004) by Mol on the PDB website."}

LitCovid-sample-Pubtator

LitCovid-sample-UniProt

LitCovid-sample-PD-IDO

{"project":"LitCovid-sample-PD-IDO","denotations":[{"id":"T23","span":{"begin":363,"end":377},"obj":"http://purl.obolibrary.org/obo/IDO_0000467"},{"id":"T24","span":{"begin":413,"end":420},"obj":"http://purl.obolibrary.org/obo/OGMS_0000031"},{"id":"T25","span":{"begin":710,"end":718},"obj":"http://purl.obolibrary.org/obo/IDO_0000607"},{"id":"T26","span":{"begin":1392,"end":1399},"obj":"http://purl.obolibrary.org/obo/IDO_0000531"},{"id":"T27","span":{"begin":1700,"end":1704},"obj":"http://purl.obolibrary.org/obo/BFO_0000029"}],"text":"Structure of ACE2\nACE2 is a 40 kb gene and it is positioned on chromosome Xp22, differently from ACE gene that is located on chromosome 17. The 18 exons of ACE2 are remarkably similar to ACE exons. The ACE2 gene depicts a large polymorphism and several novel polymorphisms of ACE2, with specific geographical distribution, have been described and associated with susceptibility to hypertension and cardiovascular disease (Burrell et al., 2013; Patel et al., 2014; Pinheiro et al., 2019).\nThe ACE2 gene codifies for a typical zinc-metallopeptidase of 805 amino acids (120 kDa), with a unique catalytic domain. Despite the high resemblance of ACE and ACE2, considerable differences exist in their substrates and products. While ACE acts as dipeptidase, ACE2 removes only a single amino acid from its substrates. Therefore, ACE2 is not active in transforming angiotensin I to angiotensin II and in inactivating bradykinin; moreover, ACE2 is insensitive to ACE inhibitors, like lisinopril and captopril (Tipnis et al., 2000; Rice et al., 2004; Turner et al., 2004).\nThese differences depend on variances in the three-dimensional structure (3D) of the two enzymes. Comparative homology modeling and crystallography contributed to shed light on ACE2 3D structure (Figure 1). Prabakaran et al. (2004) clarified the major characteristic of ACE2, which is a deep channel on the summit of the protein, hosting the catalytic domain. Specific loops, like the long loop N210-Q221 that is exclusive of ACE2, α helices and a portion of β-sheet are located around the catalytic channel. The negative charge of the channel and the presence of distinct hydrophobic regions contribute to the specificity of the binding site (Prabakaran et al., 2004). The determination of the crystal structure of the extracellular domain to 2.2-3-A resolution from Towler et al. (2004) and the model from Guy et al. (2003) showed that the catalytic domain of ACE and ACE2 are very conserved and have similar mechanisms of action. The main difference stems from the smaller ACE2 pocket, thereby lodging only a single amino acid: the crucial substitution of the Gln281 in ACE binding pocket with Arg273 in ACE2 is likely to be responsible for the steric conflict (Guy et al., 2003; Towler et al., 2004). Another surprise of the ACE2 structure was its C-terminal domain, which—differently from ACE—revealed high homology with collectrin, a renal protein, which is involved in amino acids trafficking through the membrane (Yang et al., 2017).\nFIGURE 1 Crystal structure of ACE2. The peptidase domain (PD) is in green, whereas the collectrin homology domain is enclosed in the light cyan square. The active zinc ion is showed enclosed in a red circle, whereas the glycosylation moieties are showed as cyan cubes and denoted by dashed arrows. The structures have been drawn from PDB 1R42 (Towler et al., 2004) by Mol on the PDB website."}

LitCovid-sample-PD-FMA

LitCovid-sample-PD-MONDO

{"project":"LitCovid-sample-PD-MONDO","denotations":[{"id":"T42","span":{"begin":381,"end":420},"obj":"Disease"}],"attributes":[{"id":"A42","pred":"mondo_id","subj":"T42","obj":"http://purl.obolibrary.org/obo/MONDO_0001302"}],"text":"Structure of ACE2\nACE2 is a 40 kb gene and it is positioned on chromosome Xp22, differently from ACE gene that is located on chromosome 17. The 18 exons of ACE2 are remarkably similar to ACE exons. The ACE2 gene depicts a large polymorphism and several novel polymorphisms of ACE2, with specific geographical distribution, have been described and associated with susceptibility to hypertension and cardiovascular disease (Burrell et al., 2013; Patel et al., 2014; Pinheiro et al., 2019).\nThe ACE2 gene codifies for a typical zinc-metallopeptidase of 805 amino acids (120 kDa), with a unique catalytic domain. Despite the high resemblance of ACE and ACE2, considerable differences exist in their substrates and products. While ACE acts as dipeptidase, ACE2 removes only a single amino acid from its substrates. Therefore, ACE2 is not active in transforming angiotensin I to angiotensin II and in inactivating bradykinin; moreover, ACE2 is insensitive to ACE inhibitors, like lisinopril and captopril (Tipnis et al., 2000; Rice et al., 2004; Turner et al., 2004).\nThese differences depend on variances in the three-dimensional structure (3D) of the two enzymes. Comparative homology modeling and crystallography contributed to shed light on ACE2 3D structure (Figure 1). Prabakaran et al. (2004) clarified the major characteristic of ACE2, which is a deep channel on the summit of the protein, hosting the catalytic domain. Specific loops, like the long loop N210-Q221 that is exclusive of ACE2, α helices and a portion of β-sheet are located around the catalytic channel. The negative charge of the channel and the presence of distinct hydrophobic regions contribute to the specificity of the binding site (Prabakaran et al., 2004). The determination of the crystal structure of the extracellular domain to 2.2-3-A resolution from Towler et al. (2004) and the model from Guy et al. (2003) showed that the catalytic domain of ACE and ACE2 are very conserved and have similar mechanisms of action. The main difference stems from the smaller ACE2 pocket, thereby lodging only a single amino acid: the crucial substitution of the Gln281 in ACE binding pocket with Arg273 in ACE2 is likely to be responsible for the steric conflict (Guy et al., 2003; Towler et al., 2004). Another surprise of the ACE2 structure was its C-terminal domain, which—differently from ACE—revealed high homology with collectrin, a renal protein, which is involved in amino acids trafficking through the membrane (Yang et al., 2017).\nFIGURE 1 Crystal structure of ACE2. The peptidase domain (PD) is in green, whereas the collectrin homology domain is enclosed in the light cyan square. The active zinc ion is showed enclosed in a red circle, whereas the glycosylation moieties are showed as cyan cubes and denoted by dashed arrows. The structures have been drawn from PDB 1R42 (Towler et al., 2004) by Mol on the PDB website."}

LitCovid-sample-PD-MAT

{"project":"LitCovid-sample-PD-MAT","denotations":[{"id":"T15","span":{"begin":2015,"end":2020},"obj":"http://purl.obolibrary.org/obo/MAT_0000239"}],"text":"Structure of ACE2\nACE2 is a 40 kb gene and it is positioned on chromosome Xp22, differently from ACE gene that is located on chromosome 17. The 18 exons of ACE2 are remarkably similar to ACE exons. The ACE2 gene depicts a large polymorphism and several novel polymorphisms of ACE2, with specific geographical distribution, have been described and associated with susceptibility to hypertension and cardiovascular disease (Burrell et al., 2013; Patel et al., 2014; Pinheiro et al., 2019).\nThe ACE2 gene codifies for a typical zinc-metallopeptidase of 805 amino acids (120 kDa), with a unique catalytic domain. Despite the high resemblance of ACE and ACE2, considerable differences exist in their substrates and products. While ACE acts as dipeptidase, ACE2 removes only a single amino acid from its substrates. Therefore, ACE2 is not active in transforming angiotensin I to angiotensin II and in inactivating bradykinin; moreover, ACE2 is insensitive to ACE inhibitors, like lisinopril and captopril (Tipnis et al., 2000; Rice et al., 2004; Turner et al., 2004).\nThese differences depend on variances in the three-dimensional structure (3D) of the two enzymes. Comparative homology modeling and crystallography contributed to shed light on ACE2 3D structure (Figure 1). Prabakaran et al. (2004) clarified the major characteristic of ACE2, which is a deep channel on the summit of the protein, hosting the catalytic domain. Specific loops, like the long loop N210-Q221 that is exclusive of ACE2, α helices and a portion of β-sheet are located around the catalytic channel. The negative charge of the channel and the presence of distinct hydrophobic regions contribute to the specificity of the binding site (Prabakaran et al., 2004). The determination of the crystal structure of the extracellular domain to 2.2-3-A resolution from Towler et al. (2004) and the model from Guy et al. (2003) showed that the catalytic domain of ACE and ACE2 are very conserved and have similar mechanisms of action. The main difference stems from the smaller ACE2 pocket, thereby lodging only a single amino acid: the crucial substitution of the Gln281 in ACE binding pocket with Arg273 in ACE2 is likely to be responsible for the steric conflict (Guy et al., 2003; Towler et al., 2004). Another surprise of the ACE2 structure was its C-terminal domain, which—differently from ACE—revealed high homology with collectrin, a renal protein, which is involved in amino acids trafficking through the membrane (Yang et al., 2017).\nFIGURE 1 Crystal structure of ACE2. The peptidase domain (PD) is in green, whereas the collectrin homology domain is enclosed in the light cyan square. The active zinc ion is showed enclosed in a red circle, whereas the glycosylation moieties are showed as cyan cubes and denoted by dashed arrows. The structures have been drawn from PDB 1R42 (Towler et al., 2004) by Mol on the PDB website."}

LitCovid-sample-PD-GO-BP-0

{"project":"LitCovid-sample-PD-GO-BP-0","denotations":[{"id":"T12","span":{"begin":2725,"end":2738},"obj":"http://purl.obolibrary.org/obo/GO_0070085"}],"text":"Structure of ACE2\nACE2 is a 40 kb gene and it is positioned on chromosome Xp22, differently from ACE gene that is located on chromosome 17. The 18 exons of ACE2 are remarkably similar to ACE exons. The ACE2 gene depicts a large polymorphism and several novel polymorphisms of ACE2, with specific geographical distribution, have been described and associated with susceptibility to hypertension and cardiovascular disease (Burrell et al., 2013; Patel et al., 2014; Pinheiro et al., 2019).\nThe ACE2 gene codifies for a typical zinc-metallopeptidase of 805 amino acids (120 kDa), with a unique catalytic domain. Despite the high resemblance of ACE and ACE2, considerable differences exist in their substrates and products. While ACE acts as dipeptidase, ACE2 removes only a single amino acid from its substrates. Therefore, ACE2 is not active in transforming angiotensin I to angiotensin II and in inactivating bradykinin; moreover, ACE2 is insensitive to ACE inhibitors, like lisinopril and captopril (Tipnis et al., 2000; Rice et al., 2004; Turner et al., 2004).\nThese differences depend on variances in the three-dimensional structure (3D) of the two enzymes. Comparative homology modeling and crystallography contributed to shed light on ACE2 3D structure (Figure 1). Prabakaran et al. (2004) clarified the major characteristic of ACE2, which is a deep channel on the summit of the protein, hosting the catalytic domain. Specific loops, like the long loop N210-Q221 that is exclusive of ACE2, α helices and a portion of β-sheet are located around the catalytic channel. The negative charge of the channel and the presence of distinct hydrophobic regions contribute to the specificity of the binding site (Prabakaran et al., 2004). The determination of the crystal structure of the extracellular domain to 2.2-3-A resolution from Towler et al. (2004) and the model from Guy et al. (2003) showed that the catalytic domain of ACE and ACE2 are very conserved and have similar mechanisms of action. The main difference stems from the smaller ACE2 pocket, thereby lodging only a single amino acid: the crucial substitution of the Gln281 in ACE binding pocket with Arg273 in ACE2 is likely to be responsible for the steric conflict (Guy et al., 2003; Towler et al., 2004). Another surprise of the ACE2 structure was its C-terminal domain, which—differently from ACE—revealed high homology with collectrin, a renal protein, which is involved in amino acids trafficking through the membrane (Yang et al., 2017).\nFIGURE 1 Crystal structure of ACE2. The peptidase domain (PD) is in green, whereas the collectrin homology domain is enclosed in the light cyan square. The active zinc ion is showed enclosed in a red circle, whereas the glycosylation moieties are showed as cyan cubes and denoted by dashed arrows. The structures have been drawn from PDB 1R42 (Towler et al., 2004) by Mol on the PDB website."}

LitCovid-sample-PD-HP

{"project":"LitCovid-sample-PD-HP","denotations":[{"id":"T12","span":{"begin":381,"end":393},"obj":"Phenotype"},{"id":"T13","span":{"begin":398,"end":420},"obj":"Phenotype"}],"attributes":[{"id":"A13","pred":"hp_id","subj":"T13","obj":"http://purl.obolibrary.org/obo/HP_0001626"},{"id":"A12","pred":"hp_id","subj":"T12","obj":"http://purl.obolibrary.org/obo/HP_0000822"}],"text":"Structure of ACE2\nACE2 is a 40 kb gene and it is positioned on chromosome Xp22, differently from ACE gene that is located on chromosome 17. The 18 exons of ACE2 are remarkably similar to ACE exons. The ACE2 gene depicts a large polymorphism and several novel polymorphisms of ACE2, with specific geographical distribution, have been described and associated with susceptibility to hypertension and cardiovascular disease (Burrell et al., 2013; Patel et al., 2014; Pinheiro et al., 2019).\nThe ACE2 gene codifies for a typical zinc-metallopeptidase of 805 amino acids (120 kDa), with a unique catalytic domain. Despite the high resemblance of ACE and ACE2, considerable differences exist in their substrates and products. While ACE acts as dipeptidase, ACE2 removes only a single amino acid from its substrates. Therefore, ACE2 is not active in transforming angiotensin I to angiotensin II and in inactivating bradykinin; moreover, ACE2 is insensitive to ACE inhibitors, like lisinopril and captopril (Tipnis et al., 2000; Rice et al., 2004; Turner et al., 2004).\nThese differences depend on variances in the three-dimensional structure (3D) of the two enzymes. Comparative homology modeling and crystallography contributed to shed light on ACE2 3D structure (Figure 1). Prabakaran et al. (2004) clarified the major characteristic of ACE2, which is a deep channel on the summit of the protein, hosting the catalytic domain. Specific loops, like the long loop N210-Q221 that is exclusive of ACE2, α helices and a portion of β-sheet are located around the catalytic channel. The negative charge of the channel and the presence of distinct hydrophobic regions contribute to the specificity of the binding site (Prabakaran et al., 2004). The determination of the crystal structure of the extracellular domain to 2.2-3-A resolution from Towler et al. (2004) and the model from Guy et al. (2003) showed that the catalytic domain of ACE and ACE2 are very conserved and have similar mechanisms of action. The main difference stems from the smaller ACE2 pocket, thereby lodging only a single amino acid: the crucial substitution of the Gln281 in ACE binding pocket with Arg273 in ACE2 is likely to be responsible for the steric conflict (Guy et al., 2003; Towler et al., 2004). Another surprise of the ACE2 structure was its C-terminal domain, which—differently from ACE—revealed high homology with collectrin, a renal protein, which is involved in amino acids trafficking through the membrane (Yang et al., 2017).\nFIGURE 1 Crystal structure of ACE2. The peptidase domain (PD) is in green, whereas the collectrin homology domain is enclosed in the light cyan square. The active zinc ion is showed enclosed in a red circle, whereas the glycosylation moieties are showed as cyan cubes and denoted by dashed arrows. The structures have been drawn from PDB 1R42 (Towler et al., 2004) by Mol on the PDB website."}

LitCovid-sample-GO-BP

{"project":"LitCovid-sample-GO-BP","denotations":[{"id":"T12","span":{"begin":2725,"end":2738},"obj":"http://purl.obolibrary.org/obo/GO_0070085"}],"text":"Structure of ACE2\nACE2 is a 40 kb gene and it is positioned on chromosome Xp22, differently from ACE gene that is located on chromosome 17. The 18 exons of ACE2 are remarkably similar to ACE exons. The ACE2 gene depicts a large polymorphism and several novel polymorphisms of ACE2, with specific geographical distribution, have been described and associated with susceptibility to hypertension and cardiovascular disease (Burrell et al., 2013; Patel et al., 2014; Pinheiro et al., 2019).\nThe ACE2 gene codifies for a typical zinc-metallopeptidase of 805 amino acids (120 kDa), with a unique catalytic domain. Despite the high resemblance of ACE and ACE2, considerable differences exist in their substrates and products. While ACE acts as dipeptidase, ACE2 removes only a single amino acid from its substrates. Therefore, ACE2 is not active in transforming angiotensin I to angiotensin II and in inactivating bradykinin; moreover, ACE2 is insensitive to ACE inhibitors, like lisinopril and captopril (Tipnis et al., 2000; Rice et al., 2004; Turner et al., 2004).\nThese differences depend on variances in the three-dimensional structure (3D) of the two enzymes. Comparative homology modeling and crystallography contributed to shed light on ACE2 3D structure (Figure 1). Prabakaran et al. (2004) clarified the major characteristic of ACE2, which is a deep channel on the summit of the protein, hosting the catalytic domain. Specific loops, like the long loop N210-Q221 that is exclusive of ACE2, α helices and a portion of β-sheet are located around the catalytic channel. The negative charge of the channel and the presence of distinct hydrophobic regions contribute to the specificity of the binding site (Prabakaran et al., 2004). The determination of the crystal structure of the extracellular domain to 2.2-3-A resolution from Towler et al. (2004) and the model from Guy et al. (2003) showed that the catalytic domain of ACE and ACE2 are very conserved and have similar mechanisms of action. The main difference stems from the smaller ACE2 pocket, thereby lodging only a single amino acid: the crucial substitution of the Gln281 in ACE binding pocket with Arg273 in ACE2 is likely to be responsible for the steric conflict (Guy et al., 2003; Towler et al., 2004). Another surprise of the ACE2 structure was its C-terminal domain, which—differently from ACE—revealed high homology with collectrin, a renal protein, which is involved in amino acids trafficking through the membrane (Yang et al., 2017).\nFIGURE 1 Crystal structure of ACE2. The peptidase domain (PD) is in green, whereas the collectrin homology domain is enclosed in the light cyan square. The active zinc ion is showed enclosed in a red circle, whereas the glycosylation moieties are showed as cyan cubes and denoted by dashed arrows. The structures have been drawn from PDB 1R42 (Towler et al., 2004) by Mol on the PDB website."}

LitCovid-PD-HP

{"project":"LitCovid-PD-HP","denotations":[{"id":"T12","span":{"begin":381,"end":393},"obj":"Phenotype"},{"id":"T13","span":{"begin":398,"end":420},"obj":"Phenotype"}],"attributes":[{"id":"A12","pred":"hp_id","subj":"T12","obj":"http://purl.obolibrary.org/obo/HP_0000822"},{"id":"A13","pred":"hp_id","subj":"T13","obj":"http://purl.obolibrary.org/obo/HP_0001626"}],"text":"Structure of ACE2\nACE2 is a 40 kb gene and it is positioned on chromosome Xp22, differently from ACE gene that is located on chromosome 17. The 18 exons of ACE2 are remarkably similar to ACE exons. The ACE2 gene depicts a large polymorphism and several novel polymorphisms of ACE2, with specific geographical distribution, have been described and associated with susceptibility to hypertension and cardiovascular disease (Burrell et al., 2013; Patel et al., 2014; Pinheiro et al., 2019).\nThe ACE2 gene codifies for a typical zinc-metallopeptidase of 805 amino acids (120 kDa), with a unique catalytic domain. Despite the high resemblance of ACE and ACE2, considerable differences exist in their substrates and products. While ACE acts as dipeptidase, ACE2 removes only a single amino acid from its substrates. Therefore, ACE2 is not active in transforming angiotensin I to angiotensin II and in inactivating bradykinin; moreover, ACE2 is insensitive to ACE inhibitors, like lisinopril and captopril (Tipnis et al., 2000; Rice et al., 2004; Turner et al., 2004).\nThese differences depend on variances in the three-dimensional structure (3D) of the two enzymes. Comparative homology modeling and crystallography contributed to shed light on ACE2 3D structure (Figure 1). Prabakaran et al. (2004) clarified the major characteristic of ACE2, which is a deep channel on the summit of the protein, hosting the catalytic domain. Specific loops, like the long loop N210-Q221 that is exclusive of ACE2, α helices and a portion of β-sheet are located around the catalytic channel. The negative charge of the channel and the presence of distinct hydrophobic regions contribute to the specificity of the binding site (Prabakaran et al., 2004). The determination of the crystal structure of the extracellular domain to 2.2-3-A resolution from Towler et al. (2004) and the model from Guy et al. (2003) showed that the catalytic domain of ACE and ACE2 are very conserved and have similar mechanisms of action. The main difference stems from the smaller ACE2 pocket, thereby lodging only a single amino acid: the crucial substitution of the Gln281 in ACE binding pocket with Arg273 in ACE2 is likely to be responsible for the steric conflict (Guy et al., 2003; Towler et al., 2004). Another surprise of the ACE2 structure was its C-terminal domain, which—differently from ACE—revealed high homology with collectrin, a renal protein, which is involved in amino acids trafficking through the membrane (Yang et al., 2017).\nFIGURE 1 Crystal structure of ACE2. The peptidase domain (PD) is in green, whereas the collectrin homology domain is enclosed in the light cyan square. The active zinc ion is showed enclosed in a red circle, whereas the glycosylation moieties are showed as cyan cubes and denoted by dashed arrows. The structures have been drawn from PDB 1R42 (Towler et al., 2004) by Mol on the PDB website."}

LitCovid-PubTator

LitCovid-sentences

{"project":"LitCovid-sentences","denotations":[{"id":"T54","span":{"begin":0,"end":17},"obj":"Sentence"},{"id":"T55","span":{"begin":18,"end":139},"obj":"Sentence"},{"id":"T56","span":{"begin":140,"end":197},"obj":"Sentence"},{"id":"T57","span":{"begin":198,"end":487},"obj":"Sentence"},{"id":"T58","span":{"begin":488,"end":608},"obj":"Sentence"},{"id":"T59","span":{"begin":609,"end":719},"obj":"Sentence"},{"id":"T60","span":{"begin":720,"end":809},"obj":"Sentence"},{"id":"T61","span":{"begin":810,"end":1061},"obj":"Sentence"},{"id":"T62","span":{"begin":1062,"end":1159},"obj":"Sentence"},{"id":"T63","span":{"begin":1160,"end":1268},"obj":"Sentence"},{"id":"T64","span":{"begin":1269,"end":1421},"obj":"Sentence"},{"id":"T65","span":{"begin":1422,"end":1570},"obj":"Sentence"},{"id":"T66","span":{"begin":1571,"end":1731},"obj":"Sentence"},{"id":"T67","span":{"begin":1732,"end":1994},"obj":"Sentence"},{"id":"T68","span":{"begin":1995,"end":2266},"obj":"Sentence"},{"id":"T69","span":{"begin":2267,"end":2503},"obj":"Sentence"},{"id":"T70","span":{"begin":2504,"end":2540},"obj":"Sentence"},{"id":"T71","span":{"begin":2541,"end":2656},"obj":"Sentence"},{"id":"T72","span":{"begin":2657,"end":2802},"obj":"Sentence"},{"id":"T73","span":{"begin":2803,"end":2896},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"Structure of ACE2\nACE2 is a 40 kb gene and it is positioned on chromosome Xp22, differently from ACE gene that is located on chromosome 17. The 18 exons of ACE2 are remarkably similar to ACE exons. The ACE2 gene depicts a large polymorphism and several novel polymorphisms of ACE2, with specific geographical distribution, have been described and associated with susceptibility to hypertension and cardiovascular disease (Burrell et al., 2013; Patel et al., 2014; Pinheiro et al., 2019).\nThe ACE2 gene codifies for a typical zinc-metallopeptidase of 805 amino acids (120 kDa), with a unique catalytic domain. Despite the high resemblance of ACE and ACE2, considerable differences exist in their substrates and products. While ACE acts as dipeptidase, ACE2 removes only a single amino acid from its substrates. Therefore, ACE2 is not active in transforming angiotensin I to angiotensin II and in inactivating bradykinin; moreover, ACE2 is insensitive to ACE inhibitors, like lisinopril and captopril (Tipnis et al., 2000; Rice et al., 2004; Turner et al., 2004).\nThese differences depend on variances in the three-dimensional structure (3D) of the two enzymes. Comparative homology modeling and crystallography contributed to shed light on ACE2 3D structure (Figure 1). Prabakaran et al. (2004) clarified the major characteristic of ACE2, which is a deep channel on the summit of the protein, hosting the catalytic domain. Specific loops, like the long loop N210-Q221 that is exclusive of ACE2, α helices and a portion of β-sheet are located around the catalytic channel. The negative charge of the channel and the presence of distinct hydrophobic regions contribute to the specificity of the binding site (Prabakaran et al., 2004). The determination of the crystal structure of the extracellular domain to 2.2-3-A resolution from Towler et al. (2004) and the model from Guy et al. (2003) showed that the catalytic domain of ACE and ACE2 are very conserved and have similar mechanisms of action. The main difference stems from the smaller ACE2 pocket, thereby lodging only a single amino acid: the crucial substitution of the Gln281 in ACE binding pocket with Arg273 in ACE2 is likely to be responsible for the steric conflict (Guy et al., 2003; Towler et al., 2004). Another surprise of the ACE2 structure was its C-terminal domain, which—differently from ACE—revealed high homology with collectrin, a renal protein, which is involved in amino acids trafficking through the membrane (Yang et al., 2017).\nFIGURE 1 Crystal structure of ACE2. The peptidase domain (PD) is in green, whereas the collectrin homology domain is enclosed in the light cyan square. The active zinc ion is showed enclosed in a red circle, whereas the glycosylation moieties are showed as cyan cubes and denoted by dashed arrows. The structures have been drawn from PDB 1R42 (Towler et al., 2004) by Mol on the PDB website."}

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