8BFW
The structures of Ace2 in complex with bicyclic peptide inhibitor
Summary for 8BFW
| Entry DOI | 10.2210/pdb8bfw/pdb |
| Descriptor | Processed angiotensin-converting enzyme 2, ALA-CYS-VAL-ARG-SER-HIS-CYS-SER-SER-LEU-LEU-PRO-ARG-ILE-HIS-CYS-ALA-NH2, 1-[3,5-bis(3-bromanylpropanoyl)-1,3,5-triazinan-1-yl]-3-bromanyl-propan-1-one, ... (4 entities in total) |
| Functional Keywords | cov-2-sars bind proteins, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 145868.86 |
| Authors | Brear, P.,Lulla, A.,Harman, M.,Dods, R.,Chen, L.,Bezerra, G.,Demydchuk, Y.,Stanway, S.,Hyvonen, M. (deposition date: 2022-10-27, release date: 2023-10-04, Last modification date: 2024-10-23) |
| Primary citation | Harman, M.A.J.,Stanway, S.J.,Scott, H.,Demydchuk, Y.,Bezerra, G.A.,Pellegrino, S.,Chen, L.,Brear, P.,Lulla, A.,Hyvonen, M.,Beswick, P.J.,Skynner, M.J. Structure-Guided Chemical Optimization of Bicyclic Peptide ( Bicycle ) Inhibitors of Angiotensin-Converting Enzyme 2. J.Med.Chem., 66:9881-9893, 2023 Cited by PubMed Abstract: Angiotensin-converting enzyme 2 (ACE2) is a metalloprotease that cleaves angiotensin II, a peptide substrate involved in the regulation of hypertension. Here, we identified a series of constrained bicyclic peptides, , inhibitors of human ACE2 by panning highly diverse bacteriophage display libraries. These were used to generate X-ray crystal structures which were used to inform the design of additional with increased affinity and inhibition of ACE2 enzymatic activity. This novel structural class of ACE2 inhibitors is among the most potent ACE2 inhibitors yet described , representing a valuable tool to further probe ACE2 function and for potential therapeutic utility. PubMed: 37433017DOI: 10.1021/acs.jmedchem.3c00710 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.33 Å) |
Structure validation
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