4WMF

Crystal structure of catalytically inactive MERS-CoV 3CL protease (C148A) in spacegroup P212121

4WMF の概要

• エントリーDOI: 10.2210/pdb4wmf/pdb
• 関連するPDBエントリー: 4WMD 4WME
• 分子名称: MERS-CoV 3CL protease, DI(HYDROXYETHYL)ETHER, TETRAETHYLENE GLYCOL, ... (4 entities in total)
• 機能のキーワード: mes, 3cl protease, coronavirus, hydrolase
• 由来する生物種: Middle East respiratory syndrome coronavirus
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 101574.18

構造登録者

Lountos, G.T.,Needle, D.,Waugh, D.S. (登録日: 2014-10-08, 公開日: 2015-05-13, 最終更新日: 2023-09-27)

主引用文献

Needle, D.,Lountos, G.T.,Waugh, D.S.
Structures of the Middle East respiratory syndrome coronavirus 3C-like protease reveal insights into substrate specificity.
Acta Crystallogr.,Sect.D, 71:1102-1111, 2015

PubMed Abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic virus that causes severe respiratory illness accompanied by multi-organ dysfunction, resulting in a case fatality rate of approximately 40%. As found in other coronaviruses, the majority of the positive-stranded RNA MERS-CoV genome is translated into two polyproteins, one created by a ribosomal frameshift, that are cleaved at three sites by a papain-like protease and at 11 sites by a 3C-like protease (3 CL(pro)). Since 3 CL(pro) is essential for viral replication, it is a leading candidate for therapeutic intervention. To accelerate the development of 3 CL(pro) inhibitors, three crystal structures of a catalytically inactive variant (C148A) of the MERS-CoV 3 CL(pro) enzyme were determined. The aim was to co-crystallize the inactive enzyme with a peptide substrate. Fortuitously, however, in two of the structures the C-terminus of one protomer is bound in the active site of a neighboring molecule, providing a snapshot of an enzyme-product complex. In the third structure, two of the three protomers in the asymmetric unit form a homodimer similar to that of SARS-CoV 3 CL(pro); however, the third protomer adopts a radically different conformation that is likely to correspond to a crystallographic monomer, indicative of substantial structural plasticity in the enzyme. The results presented here provide a foundation for the structure-based design of small-molecule inhibitors of the MERS-CoV 3 CL(pro) enzyme.

PubMed: 25945576
DOI: 10.1107/S1399004715003521

実験手法

X-RAY DIFFRACTION (1.97 Å)