9SPA

Apo ACE2 extracellular domain

9SPA の概要

• エントリーDOI: 10.2210/pdb9spa/pdb
• 分子名称: Processed angiotensin-converting enzyme 2, MALONIC ACID, ZINC ION, ... (4 entities in total)
• 機能のキーワード: hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 70756.66

構造登録者

Brear, P.,Hyvonen, M. (登録日: 2025-09-16, 公開日: 2026-04-08, 最終更新日: 2026-04-22)

主引用文献

Romanyuk, Z.,Bettin, G.,Brear, P.,Linciano, S.,Mazzocato, Y.,Bonadies, S.,Zanotto, I.,Mazzucco, C.,Monferone, A.,Soler, M.A.,Pasut, G.,Martin, S.,Scarso, A.,Heinis, C.,Rothenberger, S.,Hyvonen, M.,Angelini, A.
Yeast Display Technology Enables Rapid Discovery of Low-Nanomolar Macrocyclic Peptide Inhibitors of Human Angiotensin-Converting Enzyme 2.
J.Med.Chem., 69:7689-7708, 2026

PubMed Abstract: Macrocyclic peptides (MPs) are valuable molecular formats for drug development, bridging small molecules and larger biologics due to their favorable pharmacological properties. Here, we describe the discovery of low-nanomolar inhibitors of human angiotensin-converting enzyme 2 (hACE2) by quantitatively screening millions of structurally diverse disulfide-cyclized peptide ligands using yeast display technology. The most potent yeast-encoded "one-ring" and "two-ring" MP inhibit hACE2 with values of 1.9 and 1.5 nM, respectively. These inhibitory potencies are comparable to those of other cyclic peptides discovered using well-established display technologies. Crystal structures of the two MPs in complex with hACE2 reveal the adoption of either a rigid β-hairpin or a cysteine-stabilized α-helix/α-helix motif. Both MPs exhibit binding modes distinct from those of previously reported inhibitors. Thus, yeast display is a valid technology to rapidly generate MPs with desired binding properties for the development of potential therapeutics.

PubMed: 41875055
DOI: 10.1021/acs.jmedchem.5c02876

実験手法

X-RAY DIFFRACTION (1.79 Å)