7E7E

The co-crystal structure of ACE2 with Fab

7E7E の概要

• エントリーDOI: 10.2210/pdb7e7e/pdb
• 分子名称: Processed angiotensin-converting enzyme 2, h11B11-Fab, ZINC ION, ... (4 entities in total)
• 機能のキーワード: ace2 fab, antiviral protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 237932.69

構造登録者

Xiao, J.Y.,Zhang, Y. (登録日: 2021-02-26, 公開日: 2021-07-14, 最終更新日: 2024-11-20)

主引用文献

Du, Y.,Shi, R.,Zhang, Y.,Duan, X.,Li, L.,Zhang, J.,Wang, F.,Zhang, R.,Shen, H.,Wang, Y.,Wu, Z.,Peng, Q.,Pan, T.,Sun, W.,Huang, W.,Feng, Y.,Feng, H.,Xiao, J.,Tan, W.,Wang, Y.,Wang, C.,Yan, J.
A broadly neutralizing humanized ACE2-targeting antibody against SARS-CoV-2 variants.
Nat Commun, 12:5000-5000, 2021

PubMed Abstract: The successive emergences and accelerating spread of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages and evolved resistance to some ongoing clinical therapeutics increase the risks associated with the coronavirus disease 2019 (COVID-19) pandemic. An urgent intervention for broadly effective therapies to limit the morbidity and mortality of COVID-19 and future transmission events from SARS-related coronaviruses (SARSr-CoVs) is needed. Here, we isolate and humanize an angiotensin-converting enzyme-2 (ACE2)-blocking monoclonal antibody (MAb), named h11B11, which exhibits potent inhibitory activity against SARS-CoV and circulating global SARS-CoV-2 lineages. When administered therapeutically or prophylactically in the hACE2 mouse model, h11B11 alleviates and prevents SARS-CoV-2 replication and virus-induced pathological syndromes. No significant changes in blood pressure and hematology chemistry toxicology were observed after injections of multiple high dosages of h11B11 in cynomolgus monkeys. Analysis of the structures of the h11B11/ACE2 and receptor-binding domain (RBD)/ACE2 complexes shows hindrance and epitope competition of the MAb and RBD for the receptor. Together, these results suggest h11B11 as a potential therapeutic countermeasure against SARS-CoV, SARS-CoV-2, and escape variants.

PubMed: 34404805
DOI: 10.1038/s41467-021-25331-x

実験手法

X-RAY DIFFRACTION (3.8 Å)