PDBsum entry 4ztb

Hydrolase

PDB id: 4ztb

Contents

Protein chains

321 a.a.

Ligands

GOL ×10

Waters ×261

PDB id:

4ztb

Name:

Hydrolase

Title:

Crystal structure of nsp2 protease from chikungunya virus in p212121 space group at 2.59 a (4molecules/asu).

Structure:

Protease nsp2. Chain: a, b, c, d. Fragment: unp residues 1006-1326. Engineered: yes

Source:

Chikungunya virus. Chikv. Organism_taxid: 37124. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.59Å R-factor: 0.212 R-free: 0.242

Authors:

M.Narwal,S.Pratap,H.Singh,P.Kumar,S.Tomar

Key ref:

M.Narwal et al. (2018). Crystal structure of chikungunya virus nsP2 cysteine protease reveals a putative flexible loop blocking its active site. Int J Biol Macromol, 116, 451-462. PubMed id: 29730006 DOI: 10.1016/j.ijbiomac.2018.05.007

Date:

14-May-15 Release date: 15-Jun-16

Protein chains

A6MH22  (A6MH22_CHIKV) -  Polyprotein P1234 from Chikungunya virus

Seq: 2474 a.a.

Struc: 321 a.a.

Enzyme reactions

• Enzyme class 1: E.C.2.7.7.19 - polynucleotide adenylyltransferase.
• Reaction: RNA(n) + ATP = RNA(n)-3'-adenine ribonucleotide + diphosphate
• Enzyme class 2: E.C.3.1.3.84 - ADP-ribose 1''-phosphate phosphatase.
• Reaction: ADP-alpha-D-ribose 1''-phosphate + H2O = ADP-D-ribose + phosphate
• Enzyme class 3: E.C.3.6.1.15 - nucleoside-triphosphate phosphatase.
• Reaction: a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + phosphate + H⁺
• Enzyme class 4: E.C.3.6.1.74 - mRNA 5'-phosphatase.
• Reaction: a 5'-end triphospho-ribonucleoside in mRNA + H2O = a 5'-end diphospho- ribonucleoside in mRNA + phosphate + H⁺
• Enzyme class 5: E.C.3.6.4.13 - Rna helicase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.ijbiomac.2018.05.007

Int J Biol Macromol 116:451-462 (2018)

PubMed id: 29730006

Crystal structure of chikungunya virus nsP2 cysteine protease reveals a putative flexible loop blocking its active site.

M.Narwal, H.Singh, S.Pratap, A.Malik, R.J.Kuhn, P.Kumar, S.Tomar.

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 K_m 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.