Document Detail


Molecular Modeling and Analysis of Hepatitis E Virus (HEV) Papain-Like Cysteine Protease.
MedLine Citation:
PMID:  24321124     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The biochemical or biophysical characterization of a papain-like cysteine protease in HEV ORF1-encoded polyprotein still remains elusive. Very recently, we have demonstrated the indispensability of ORF1 protease-domain cysteines and histidines in HEV replication, ex vivo (Parvez, Virus Res., 2013). In this report, the polyprotein partial sequences of HEV strains and genetically-related RNA viruses were analyzed, in silico. Employing the consensus-prediction results of RUBV-p(150) protease as structural-template, a 3D model of HEV protease was deduced. Similar to RUBV, a 'papain-like β-barrel fold' structurally confirmed the classification of HEV-protease. Further, we recognized a catalytic 'Cys434-His443' dyad homologue of RUBV-p(150) (Cys1152-His1273) and FMDV-L(pro) (Cys51-His148) in line with our previous mutational analysis that showed essentiality of 'His443' but not 'His590' in HEV viability. Moreover, a RUBV 'Zn(2+) binding motif' (Cys1167-Cys1175-Cys1178-Cys1225-Cys1227) equivalent of HEV was identified as 'Cys457-His458-Cys459 and Cys481-Cys483' residues within the 'β-barrel fold'. Notably, unlike RUBV, 'His458' also clustered therein, that was in conformity with the consensus cysteine protease 'Zn(2+)-binding motif'. By homology, we also proposed an overlapping 'Ca(2+)-binding site' 'D-X-[DNS]-[ILVFYW]-[DEN]-G-[GP]-XX-DE' signature, and a 'proline-rich motif' interacting 'tryptophan (W437-W472)'module in the modeled structure. Our analysis of the predicted model therefore, warrants critical roles of the 'catalytic dyad' and 'divalent metal-binding motifs' in HEV protease structural-integrity, ORF1 self-processing, and RNA replication. This however, needs further experimental validations.
Authors:
Mohammad Khalid Parvez; Azmat Ali Khan
Related Documents :
24251094 - Mechanisms of heparanase inhibition by the heparan sulfate mimetic pg545 and three stru...
24449904 - Comprehensive structural model of the mechanochemical cycle of a mitotic motor highligh...
23667794 - Using azido analogue of s-adenosyl-l-methionine for bioorthogonal profiling of protein ...
23913684 - The linker region plays a regulatory role in assembly and activity of the vps4 aaa atpase.
20156684 - Structural characteristics and antioxidant activities of the extracellular polysacchari...
21845384 - Extracellular metalloproteases from bacteria.
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-12-6
Journal Detail:
Title:  Virus research     Volume:  -     ISSN:  1872-7492     ISO Abbreviation:  Virus Res.     Publication Date:  2013 Dec 
Date Detail:
Created Date:  2013-12-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8410979     Medline TA:  Virus Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013. Published by Elsevier B.V.
Affiliation:
Departments of Pharmacognosy. Electronic address: Khalid_parve@yahoo.com.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Features and treatment modality of iliopsoas abscess and its outcome: a 6-year hospital-based study.
Next Document:  Anti-obesity activity of hen egg anti-lipase immunoglobulin yolk, a novel pancreatic lipase inhibito...