2Z3C

A Mechanistic view of Enzyme Inhibition and Peptide Hydrolysis in the Active Site of the SARS-CoV 3C-Like peptidase

2Z3C の概要

• エントリーDOI: 10.2210/pdb2z3c/pdb
• 関連するPDBエントリー: 2Z3D
• 関連するBIRD辞書のPRD_ID: PRD_000250
• 分子名称: Replicase polyprotein 1ab (pp1ab), inhibitor, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: beta barrels, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: SARS coronavirus; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 34570.51

構造登録者

Yin, J. (登録日: 2007-06-04, 公開日: 2007-07-03, 最終更新日: 2023-11-15)

主引用文献

Yin, J.,Niu, C.,Cherney, M.M.,Zhang, J.,Huitema, C.,Eltis, L.D.,Vederas, J.C.,James, M.N.
A mechanistic view of enzyme inhibition and peptide hydrolysis in the active site of the SARS-CoV 3C-like peptidase
J.Mol.Biol., 371:1060-1074, 2007

PubMed Abstract: The 3C-like main peptidase 3CL(pro) is a viral polyprotein processing enzyme essential for the viability of the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV). While it is generalized that 3CL(pro) and the structurally related 3C(pro) viral peptidases cleave their substrates via a mechanism similar to that underlying the peptide hydrolysis by chymotrypsin-like serine proteinases (CLSPs), some of the hypothesized key intermediates have not been structurally characterized. Here, we present three crystal structures of SARS 3CL(pro) in complex with each of two members of a new class of peptide-based phthalhydrazide inhibitors. Both inhibitors form an unusual thiiranium ring with the nucleophilic sulfur atom of Cys145, trapping the enzyme's catalytic residues in configurations similar to the intermediate states proposed to exist during the hydrolysis of native substrates. Most significantly, our crystallographic data are consistent with a scenario in which a water molecule, possibly via indirect coordination from the carbonyl oxygen of Thr26, has initiated nucleophilic attack on the enzyme-bound inhibitor. Our data suggest that this structure resembles that of the proposed tetrahedral intermediate during the deacylation step of normal peptidyl cleavage.

PubMed: 17599357
DOI: 10.1016/j.jmb.2007.06.001

実験手法

X-RAY DIFFRACTION (1.79 Å)