Universität zu Köln

Lei, Jian ORCID: 0000-0001-9394-8236, Mesters, Jeroen R., Drosten, Christian, Anemueller, Stefan, Ma, Qingjun and Hilgenfeld, Rolf (2014). Crystal structure of the papain-like protease of MERS coronavirus reveals unusual, potentially druggable active-site features. Antiviral Res., 109. S. 72 - 83. AMSTERDAM: ELSEVIER SCIENCE BV. ISSN 1872-9096

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Abstract

The Middle-East Respiratory Syndrome coronavirus (MERS-CoV) causes severe acute pneumonia and renal failure. The MERS-CoV papain-like protease (PLpro) is a potential target for the development of antiviral drugs. To facilitate these efforts, we determined the three-dimensional structure of the enzyme by X-ray crystallography. The molecule consists of a ubiquitin-like domain and a catalytic core domain. The catalytic domain displays an extended right-hand fold with a zinc ribbon and embraces a solvent-exposed substrate-binding region. The overall structure of the MERS-CoV PLpro is similar to that of the corresponding SARS-CoV enzyme, but the architecture of the oxyanion hole and of the S3 as well as the S5 specificity sites differ from the latter. These differences are the likely reason for reduced in vitro peptide hydrolysis and deubiquitinating activities of the MERS-CoV PLpro, compared to the homologous enzyme from the SARS coronavirus. Introduction of a side-chain capable of oxyanion stabilization through the Leu106Trp mutation greatly enhances the in vitro catalytic activity of the MERS-CoV PLpro. The unique features observed in the crystal structure of the MERS-CoV PLpro should allow the design of antivirals that would not interfere with host ubiquitin-specific proteases. (C) 2014 The Authors. Published by Elsevier B.V.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lei, Jian UNSPECIFIED orcid.org/0000-0001-9394-8236 UNSPECIFIED Mesters, Jeroen R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Drosten, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Anemueller, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Ma, Qingjun UNSPECIFIED UNSPECIFIED UNSPECIFIED Hilgenfeld, Rolf UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-430260
DOI:	10.1016/j.antiviral.2014.06.011
Journal or Publication Title:	Antiviral Res.
Volume:	109
Page Range:	S. 72 - 83
Date:	2014
Publisher:	ELSEVIER SCIENCE BV
Place of Publication:	AMSTERDAM
ISSN:	1872-9096
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RESPIRATORY-SYNDROME-CORONAVIRUS; DEUBIQUITINATING ENZYME; MAIN PROTEASE; UBIQUITIN RECOGNITION; DROMEDARY CAMELS; SARS; PROTEINASE; INHIBITORS; COMPLEX; DOMAIN Multiple languages Pharmacology & Pharmacy; Virology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43026