| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T261 |
0-139 |
Sentence |
denotes |
It is known that the catalytic cleft of ACE2 consists of two peptidase subdomains: one membrane-distal and the other one membrane-proximal. |
| T262 |
140-260 |
Sentence |
denotes |
Their weak interactions are consistent with the ability to transition from open to the closed ACE2 conformation [28,90]. |
| T263 |
261-536 |
Sentence |
denotes |
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]. |
| T264 |
537-827 |
Sentence |
denotes |
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]. |
| T265 |
828-1008 |
Sentence |
denotes |
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]. |
| T266 |
1009-1253 |
Sentence |
denotes |
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. |
| T267 |
1254-1510 |
Sentence |
denotes |
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]. |
| T268 |
1511-1778 |
Sentence |
denotes |
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]. |
| T269 |
1779-1981 |
Sentence |
denotes |
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]. |
