8BN1

The structures of Ace2 in complex with bicyclic peptide inhibitor

8BN1 の概要

• エントリーDOI: 10.2210/pdb8bn1/pdb
• 分子名称: Processed angiotensin-converting enzyme 2, ALA-CYS-VAL-ARG-SER-4PH-CYS-SER-SER-LEU-LEU-PRO-ARG-ILE-HIS-CYS-ALA-NH2, ZINC ION, ... (5 entities in total)
• 機能のキーワード: cov-2-sars bind proteins, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 146111.20

構造登録者

Brear, P.,Lulla, A.,Harman, M.,Dods, R.,Chen, L.,Bezerra, G.,Demydchuk, Y.,Stanway, S.,Hyvonen, M. (登録日: 2022-11-11, 公開日: 2023-09-20, 最終更新日: 2024-11-13)

主引用文献

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

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: 37433017
DOI: 10.1021/acs.jmedchem.3c00710

実験手法

X-RAY DIFFRACTION (2.61 Å)