7wpc
The second RBD of SARS-CoV-2 Omicron Variant in complexed with RBD-ACE2The second RBD of SARS-CoV-2 Omicron Variant in complexed with RBD-ACE2
Structural highlights
FunctionACE2_HUMAN Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin-13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. In case of human coronaviruses SARS and HCoV-NL63 infections, serve as functional receptor for the spike glycoprotein of both coronaviruses.[1] [2] [3] Publication Abstract from PubMedThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has become the dominant infective strain. We report the structures of the Omicron spike trimer on its own and in complex with angiotensin-converting enzyme 2 (ACE2) or an anti-Omicron antibody. Most Omicron mutations are located on the surface of the spike protein and change binding epitopes to many current antibodies. In the ACE2-binding site, compensating mutations strengthen receptor binding domain (RBD) binding to ACE2. Both the RBD and the apo form of the Omicron spike trimer are thermodynamically unstable. An unusual RBD-RBD interaction in the ACE2-spike complex supports the open conformation and further reinforces ACE2 binding to the spike trimer. A broad-spectrum therapeutic antibody, JMB2002, which has completed a phase 1 clinical trial, maintains neutralizing activity against Omicron. JMB2002 binds to RBD differently from other characterized antibodies and inhibits ACE2 binding. Structures of the Omicron spike trimer with ACE2 and an anti-Omicron antibody.,Yin W, Xu Y, Xu P, Cao X, Wu C, Gu C, He X, Wang X, Huang S, Yuan Q, Wu K, Hu W, Huang Z, Liu J, Wang Z, Jia F, Xia K, Liu P, Wang X, Song B, Zheng J, Jiang H, Cheng X, Jiang Y, Deng SJ, Xu HE Science. 2022 Mar 4;375(6584):1048-1053. doi: 10.1126/science.abn8863. Epub 2022 , Feb 8. PMID:35133176[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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