PMC:7408073 / 53837-55818 JSON TXT

Annnotations TAB JSON ListView MergeView

LitCovid-PD-FMA-UBERON

{"project":"LitCovid-PD-FMA-UBERON","denotations":[{"id":"T369","span":{"begin":1042,"end":1054},"obj":"Body_part"},{"id":"T370","span":{"begin":1042,"end":1046},"obj":"Body_part"},{"id":"T371","span":{"begin":1097,"end":1104},"obj":"Body_part"},{"id":"T372","span":{"begin":1171,"end":1178},"obj":"Body_part"},{"id":"T373","span":{"begin":1237,"end":1252},"obj":"Body_part"},{"id":"T374","span":{"begin":1439,"end":1447},"obj":"Body_part"},{"id":"T375","span":{"begin":1524,"end":1528},"obj":"Body_part"},{"id":"T376","span":{"begin":1536,"end":1543},"obj":"Body_part"},{"id":"T377","span":{"begin":1721,"end":1729},"obj":"Body_part"},{"id":"T378","span":{"begin":1967,"end":1975},"obj":"Body_part"}],"attributes":[{"id":"A369","pred":"fma_id","subj":"T369","obj":"http://purl.org/sig/ont/fma/fma67653"},{"id":"A370","pred":"fma_id","subj":"T370","obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"A371","pred":"fma_id","subj":"T371","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A372","pred":"fma_id","subj":"T372","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A373","pred":"fma_id","subj":"T373","obj":"http://purl.org/sig/ont/fma/fma63841"},{"id":"A374","pred":"fma_id","subj":"T374","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A375","pred":"fma_id","subj":"T375","obj":"http://purl.org/sig/ont/fma/fma9712"},{"id":"A376","pred":"fma_id","subj":"T376","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A377","pred":"fma_id","subj":"T377","obj":"http://purl.org/sig/ont/fma/fma67257"},{"id":"A378","pred":"fma_id","subj":"T378","obj":"http://purl.org/sig/ont/fma/fma67257"}],"text":"It is known that the catalytic cleft of ACE2 consists of two peptidase subdomains: one membrane-distal and the other one membrane-proximal. Their weak interactions are consistent with the ability to transition from open to the closed ACE2 conformation [28,90]. Indeed, the two subdomains undergo a large hinge-bending motion in which membrane-proximal subdomain remains almost unchanged, while membrane-distal subdomain moves to close the distance between the two subdomains, mimicking the opening/closing movement of a clam shell [90]. ACE2 open conformation likely reflects free state of the enzyme available to catch substrates (or inhibitors), then, when the ACE2 receptor binds to a substrate, the membrane-distal subdomain closes around the substrate (or the inhibitor), finally performing the enzymatic activity [24,90]. Interestingly, in cryo–electron microscopy structures of full-length human ACE2, only the closed/substrate-bound conformation of ACE2 was observed in the spike-ACE2 complexes [28]. Since human ACE2 is assembled on cell surface as a homodimer [28], binding of the spike protein trimer onto ACE2 dimer suggests simultaneous binding of two spike protein trimers to substrate-bound conformer of ACE2 homodimer on plasma membrane. The spike binding sites on ACE2 homodimer are localized above the membrane-distal peptidase subdomain of each ACE2 monomer, nevertheless neither ACE2 shedding nor ACE2 binding to spike proteins have been shown to inhibit ACE2 enzymatic activity [16,17,24]. On the other hand, the S-protein-binding region of membrane-distal ACE2 subdomain is not significantly perturbed by the receptor conformational changes and maintains the ability to associate with soluble spike proteins independently on open/closed conformations [24]. Interestingly, an ACE2 specific inhibitor (MLN-4760) has been shown to induce the closed (inhibitor-bound) ACE2 structure [90] and to retain its inhibitory effects on sACE2 bound to spike proteins [24]."}

LitCovid-PD-UBERON

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T120","span":{"begin":525,"end":530},"obj":"Body_part"},{"id":"T121","span":{"begin":1524,"end":1528},"obj":"Body_part"}],"attributes":[{"id":"A120","pred":"uberon_id","subj":"T120","obj":"http://purl.obolibrary.org/obo/UBERON_0006612"},{"id":"A121","pred":"uberon_id","subj":"T121","obj":"http://purl.obolibrary.org/obo/UBERON_0002398"}],"text":"It is known that the catalytic cleft of ACE2 consists of two peptidase subdomains: one membrane-distal and the other one membrane-proximal. Their weak interactions are consistent with the ability to transition from open to the closed ACE2 conformation [28,90]. Indeed, the two subdomains undergo a large hinge-bending motion in which membrane-proximal subdomain remains almost unchanged, while membrane-distal subdomain moves to close the distance between the two subdomains, mimicking the opening/closing movement of a clam shell [90]. ACE2 open conformation likely reflects free state of the enzyme available to catch substrates (or inhibitors), then, when the ACE2 receptor binds to a substrate, the membrane-distal subdomain closes around the substrate (or the inhibitor), finally performing the enzymatic activity [24,90]. Interestingly, in cryo–electron microscopy structures of full-length human ACE2, only the closed/substrate-bound conformation of ACE2 was observed in the spike-ACE2 complexes [28]. Since human ACE2 is assembled on cell surface as a homodimer [28], binding of the spike protein trimer onto ACE2 dimer suggests simultaneous binding of two spike protein trimers to substrate-bound conformer of ACE2 homodimer on plasma membrane. The spike binding sites on ACE2 homodimer are localized above the membrane-distal peptidase subdomain of each ACE2 monomer, nevertheless neither ACE2 shedding nor ACE2 binding to spike proteins have been shown to inhibit ACE2 enzymatic activity [16,17,24]. On the other hand, the S-protein-binding region of membrane-distal ACE2 subdomain is not significantly perturbed by the receptor conformational changes and maintains the ability to associate with soluble spike proteins independently on open/closed conformations [24]. Interestingly, an ACE2 specific inhibitor (MLN-4760) has been shown to induce the closed (inhibitor-bound) ACE2 structure [90] and to retain its inhibitory effects on sACE2 bound to spike proteins [24]."}

LitCovid-PubTator

LitCovid-PD-MONDO

{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T311","span":{"begin":520,"end":524},"obj":"Disease"}],"attributes":[{"id":"A311","pred":"mondo_id","subj":"T311","obj":"http://purl.obolibrary.org/obo/MONDO_0011948"}],"text":"It is known that the catalytic cleft of ACE2 consists of two peptidase subdomains: one membrane-distal and the other one membrane-proximal. Their weak interactions are consistent with the ability to transition from open to the closed ACE2 conformation [28,90]. Indeed, the two subdomains undergo a large hinge-bending motion in which membrane-proximal subdomain remains almost unchanged, while membrane-distal subdomain moves to close the distance between the two subdomains, mimicking the opening/closing movement of a clam shell [90]. ACE2 open conformation likely reflects free state of the enzyme available to catch substrates (or inhibitors), then, when the ACE2 receptor binds to a substrate, the membrane-distal subdomain closes around the substrate (or the inhibitor), finally performing the enzymatic activity [24,90]. Interestingly, in cryo–electron microscopy structures of full-length human ACE2, only the closed/substrate-bound conformation of ACE2 was observed in the spike-ACE2 complexes [28]. Since human ACE2 is assembled on cell surface as a homodimer [28], binding of the spike protein trimer onto ACE2 dimer suggests simultaneous binding of two spike protein trimers to substrate-bound conformer of ACE2 homodimer on plasma membrane. The spike binding sites on ACE2 homodimer are localized above the membrane-distal peptidase subdomain of each ACE2 monomer, nevertheless neither ACE2 shedding nor ACE2 binding to spike proteins have been shown to inhibit ACE2 enzymatic activity [16,17,24]. On the other hand, the S-protein-binding region of membrane-distal ACE2 subdomain is not significantly perturbed by the receptor conformational changes and maintains the ability to associate with soluble spike proteins independently on open/closed conformations [24]. Interestingly, an ACE2 specific inhibitor (MLN-4760) has been shown to induce the closed (inhibitor-bound) ACE2 structure [90] and to retain its inhibitory effects on sACE2 bound to spike proteins [24]."}

LitCovid-PD-CLO

LitCovid-PD-CHEBI

{"project":"LitCovid-PD-CHEBI","denotations":[{"id":"T75","span":{"begin":635,"end":645},"obj":"Chemical"},{"id":"T47611","span":{"begin":765,"end":774},"obj":"Chemical"},{"id":"T93730","span":{"begin":851,"end":859},"obj":"Chemical"},{"id":"T82543","span":{"begin":1097,"end":1104},"obj":"Chemical"},{"id":"T74998","span":{"begin":1171,"end":1178},"obj":"Chemical"},{"id":"T37661","span":{"begin":1439,"end":1447},"obj":"Chemical"},{"id":"T59859","span":{"begin":1536,"end":1543},"obj":"Chemical"},{"id":"T68655","span":{"begin":1721,"end":1729},"obj":"Chemical"},{"id":"T22243","span":{"begin":1811,"end":1820},"obj":"Chemical"},{"id":"T66791","span":{"begin":1869,"end":1878},"obj":"Chemical"},{"id":"T85","span":{"begin":1967,"end":1975},"obj":"Chemical"}],"attributes":[{"id":"A25811","pred":"chebi_id","subj":"T75","obj":"http://purl.obolibrary.org/obo/CHEBI_35222"},{"id":"A37201","pred":"chebi_id","subj":"T47611","obj":"http://purl.obolibrary.org/obo/CHEBI_35222"},{"id":"A6746","pred":"chebi_id","subj":"T93730","obj":"http://purl.obolibrary.org/obo/CHEBI_10545"},{"id":"A52184","pred":"chebi_id","subj":"T82543","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A51112","pred":"chebi_id","subj":"T74998","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A62553","pred":"chebi_id","subj":"T37661","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A78840","pred":"chebi_id","subj":"T59859","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A54798","pred":"chebi_id","subj":"T68655","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"},{"id":"A55397","pred":"chebi_id","subj":"T22243","obj":"http://purl.obolibrary.org/obo/CHEBI_35222"},{"id":"A27542","pred":"chebi_id","subj":"T66791","obj":"http://purl.obolibrary.org/obo/CHEBI_35222"},{"id":"A41621","pred":"chebi_id","subj":"T85","obj":"http://purl.obolibrary.org/obo/CHEBI_36080"}],"text":"It is known that the catalytic cleft of ACE2 consists of two peptidase subdomains: one membrane-distal and the other one membrane-proximal. Their weak interactions are consistent with the ability to transition from open to the closed ACE2 conformation [28,90]. Indeed, the two subdomains undergo a large hinge-bending motion in which membrane-proximal subdomain remains almost unchanged, while membrane-distal subdomain moves to close the distance between the two subdomains, mimicking the opening/closing movement of a clam shell [90]. ACE2 open conformation likely reflects free state of the enzyme available to catch substrates (or inhibitors), then, when the ACE2 receptor binds to a substrate, the membrane-distal subdomain closes around the substrate (or the inhibitor), finally performing the enzymatic activity [24,90]. Interestingly, in cryo–electron microscopy structures of full-length human ACE2, only the closed/substrate-bound conformation of ACE2 was observed in the spike-ACE2 complexes [28]. Since human ACE2 is assembled on cell surface as a homodimer [28], binding of the spike protein trimer onto ACE2 dimer suggests simultaneous binding of two spike protein trimers to substrate-bound conformer of ACE2 homodimer on plasma membrane. The spike binding sites on ACE2 homodimer are localized above the membrane-distal peptidase subdomain of each ACE2 monomer, nevertheless neither ACE2 shedding nor ACE2 binding to spike proteins have been shown to inhibit ACE2 enzymatic activity [16,17,24]. On the other hand, the S-protein-binding region of membrane-distal ACE2 subdomain is not significantly perturbed by the receptor conformational changes and maintains the ability to associate with soluble spike proteins independently on open/closed conformations [24]. Interestingly, an ACE2 specific inhibitor (MLN-4760) has been shown to induce the closed (inhibitor-bound) ACE2 structure [90] and to retain its inhibitory effects on sACE2 bound to spike proteins [24]."}

LitCovid-sentences

{"project":"LitCovid-sentences","denotations":[{"id":"T261","span":{"begin":0,"end":139},"obj":"Sentence"},{"id":"T262","span":{"begin":140,"end":260},"obj":"Sentence"},{"id":"T263","span":{"begin":261,"end":536},"obj":"Sentence"},{"id":"T264","span":{"begin":537,"end":827},"obj":"Sentence"},{"id":"T265","span":{"begin":828,"end":1008},"obj":"Sentence"},{"id":"T266","span":{"begin":1009,"end":1253},"obj":"Sentence"},{"id":"T267","span":{"begin":1254,"end":1510},"obj":"Sentence"},{"id":"T268","span":{"begin":1511,"end":1778},"obj":"Sentence"},{"id":"T269","span":{"begin":1779,"end":1981},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"It is known that the catalytic cleft of ACE2 consists of two peptidase subdomains: one membrane-distal and the other one membrane-proximal. Their weak interactions are consistent with the ability to transition from open to the closed ACE2 conformation [28,90]. Indeed, the two subdomains undergo a large hinge-bending motion in which membrane-proximal subdomain remains almost unchanged, while membrane-distal subdomain moves to close the distance between the two subdomains, mimicking the opening/closing movement of a clam shell [90]. ACE2 open conformation likely reflects free state of the enzyme available to catch substrates (or inhibitors), then, when the ACE2 receptor binds to a substrate, the membrane-distal subdomain closes around the substrate (or the inhibitor), finally performing the enzymatic activity [24,90]. Interestingly, in cryo–electron microscopy structures of full-length human ACE2, only the closed/substrate-bound conformation of ACE2 was observed in the spike-ACE2 complexes [28]. Since human ACE2 is assembled on cell surface as a homodimer [28], binding of the spike protein trimer onto ACE2 dimer suggests simultaneous binding of two spike protein trimers to substrate-bound conformer of ACE2 homodimer on plasma membrane. The spike binding sites on ACE2 homodimer are localized above the membrane-distal peptidase subdomain of each ACE2 monomer, nevertheless neither ACE2 shedding nor ACE2 binding to spike proteins have been shown to inhibit ACE2 enzymatic activity [16,17,24]. On the other hand, the S-protein-binding region of membrane-distal ACE2 subdomain is not significantly perturbed by the receptor conformational changes and maintains the ability to associate with soluble spike proteins independently on open/closed conformations [24]. Interestingly, an ACE2 specific inhibitor (MLN-4760) has been shown to induce the closed (inhibitor-bound) ACE2 structure [90] and to retain its inhibitory effects on sACE2 bound to spike proteins [24]."}

2_test

{"project":"2_test","denotations":[{"id":"32708755-32132184-20678843","span":{"begin":253,"end":255},"obj":"32132184"},{"id":"32708755-15791205-20678844","span":{"begin":820,"end":822},"obj":"15791205"},{"id":"32708755-32132184-20678845","span":{"begin":1004,"end":1006},"obj":"32132184"},{"id":"32708755-32132184-20678846","span":{"begin":1071,"end":1073},"obj":"32132184"},{"id":"32708755-18490652-20678847","span":{"begin":1503,"end":1505},"obj":"18490652"},{"id":"32708755-15791205-20678848","span":{"begin":1506,"end":1508},"obj":"15791205"},{"id":"32708755-15791205-20678849","span":{"begin":1774,"end":1776},"obj":"15791205"},{"id":"32708755-15791205-20678850","span":{"begin":1977,"end":1979},"obj":"15791205"}],"text":"It is known that the catalytic cleft of ACE2 consists of two peptidase subdomains: one membrane-distal and the other one membrane-proximal. Their weak interactions are consistent with the ability to transition from open to the closed ACE2 conformation [28,90]. Indeed, the two subdomains undergo a large hinge-bending motion in which membrane-proximal subdomain remains almost unchanged, while membrane-distal subdomain moves to close the distance between the two subdomains, mimicking the opening/closing movement of a clam shell [90]. ACE2 open conformation likely reflects free state of the enzyme available to catch substrates (or inhibitors), then, when the ACE2 receptor binds to a substrate, the membrane-distal subdomain closes around the substrate (or the inhibitor), finally performing the enzymatic activity [24,90]. Interestingly, in cryo–electron microscopy structures of full-length human ACE2, only the closed/substrate-bound conformation of ACE2 was observed in the spike-ACE2 complexes [28]. Since human ACE2 is assembled on cell surface as a homodimer [28], binding of the spike protein trimer onto ACE2 dimer suggests simultaneous binding of two spike protein trimers to substrate-bound conformer of ACE2 homodimer on plasma membrane. The spike binding sites on ACE2 homodimer are localized above the membrane-distal peptidase subdomain of each ACE2 monomer, nevertheless neither ACE2 shedding nor ACE2 binding to spike proteins have been shown to inhibit ACE2 enzymatic activity [16,17,24]. On the other hand, the S-protein-binding region of membrane-distal ACE2 subdomain is not significantly perturbed by the receptor conformational changes and maintains the ability to associate with soluble spike proteins independently on open/closed conformations [24]. Interestingly, an ACE2 specific inhibitor (MLN-4760) has been shown to induce the closed (inhibitor-bound) ACE2 structure [90] and to retain its inhibitory effects on sACE2 bound to spike proteins [24]."}

PMC:7408073 / 53837-55818 JSONTXT

Annnotations TAB JSON ListView MergeView

PMC:7408073 / 53837-55818 JSON TXT