9EYA

Complex of a mutant of the SARS-CoV-2 main protease Mpro with the nsp4/5 substrate peptide (soaking).

9EYA の概要

• エントリーDOI: 10.2210/pdb9eya/pdb
• 関連するPDBエントリー: 9EX8 9EXU
• 分子名称: Non-structural protein 7, THR-SER-ALA-VAL-LEU-GLN-SER-GLY-PHE-ARG-LYS (3 entities in total)
• 機能のキーワード: sars-cov-2, main protease, nsp5, cys-peptidase, 3clpro, hydrolase
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 34963.82

構造登録者

Battistutta, R.,Fornasier, E.,Giachin, G. (登録日: 2024-04-09, 公開日: 2025-02-12)

主引用文献

Fornasier, E.,Fabbian, S.,Shehi, H.,Enderle, J.,Gatto, B.,Volpin, D.,Biondi, B.,Bellanda, M.,Giachin, G.,Sosic, A.,Battistutta, R.
Allostery in homodimeric SARS-CoV-2 main protease.
Commun Biol, 7:1435-1435, 2024

PubMed Abstract: Many enzymes work as homodimers with two distant catalytic sites, but the reason for this choice is often not clear. For the main protease M of SARS-CoV-2, dimerization is essential for function and plays a regulatory role during the coronaviral replication process. Here, to analyze a possible allosteric mechanism, we use X-ray crystallography, native mass spectrometry, isothermal titration calorimetry, and activity assays to study the interaction of M with three peptide substrates. Crystal structures show how the plasticity of M is exploited to face differences in the sequences of the natural substrates. Importantly, unlike in the free form, the M dimer in complex with these peptides is asymmetric and the structures of the substrates nsp5/6 and nsp14/15 bound to a single subunit show allosteric communications between active sites. We identified arginines 4 and 298 as key elements in the transition from symmetric to asymmetric dimers. Kinetic data allowed the identification of positive cooperativity based on the increase in the processing efficiency (kinetic allostery) and not on the better binding of the substrates (thermodynamic allostery). At the physiological level, this allosteric behavior may be justified by the need to regulate the processing of viral polyproteins in time and space.

PubMed: 39496839
DOI: 10.1038/s42003-024-07138-w

実験手法

X-RAY DIFFRACTION (1.7 Å)