Skip navigation
Please use this identifier to cite or link to this item:
Title: Crystal structure of chikungunya virus nsP2 cysteine protease reveals a putative flexible loop blocking its active site
Authors: Narwal M.
Singh H.
Pratap S.
Malik A.
Kuhn R.J.
Kumar, Pravindra R.Manish
Tomar, Shailly
Published in: International Journal of Biological Macromolecules
Abstract: Chikungunya virus (CHIKV), a mosquito-borne pathogenic alphavirus is a growing public health threat. No vaccines or antiviral drug is currently available in the market for chikungunya treatment. nsP2pro, the viral cysteine protease, carries out an essential function of nonstructural polyprotein processing and forms four nonstructural proteins (nsPs) that makes the replication complex, hence constitute a promising drug target. In this study, crystal structure of nsP2pro has been determined at 2.59 Å which reveals that the protein consists of two subdomains: an N-terminal protease subdomain and a C-terminal methyltransferase subdomain. Structural comparison of CHIKV nsP2pro with structures of other alphavirus nsP2 advances that the substrate binding cleft is present at the interface of two subdomains. Additionally, structure insights revealed that access to the active site and substrate binding cleft is blocked by a flexible interdomain loop in CHIKV nsP2pro. This loop contains His548, the catalytic residue, and Trp549 and Asn547, the residues predicted to bind substrate. Interestingly, mutation of Asn547 leads to three-fold increase in Km confirming that Asn547 plays important role in substrate binding and recognition. This study presents the detailed molecular analysis and signifies the substrate specificity residues of CHIKV nsP2pro, which will be beneficial for structure-based drug design and optimization of CHIKV protease inhibitors. © 2018 Elsevier B.V.
Citation: International Journal of Biological Macromolecules(2018), 116(): 451-462
Issue Date: 2018
Publisher: Elsevier B.V.
Keywords: Active site blockade
Chikungunya virus
Cysteine protease
FRET assay
Plus-strand RNA virus
ISSN: 1418130
Author Scopus IDs: 49461618600
Author Affiliations: Narwal, M., Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India
Singh, H., Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India
Pratap, S., Depart
Funding Details: This project was financed by Department of Biotechnology ( DBT ) Government of India (Grant ref. number BT/PR9670/MED/29/807/2013 ).
Corresponding Author: Tomar, S.; Department of Biotechnology, Indian Institute of Technology RoorkeeIndia; email:
Appears in Collections:Journal Publications [BT]

Files in This Item:
There are no files associated with this item.
Show full item record

Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.