PDBsum entry 2hwk

Hydrolase

PDB id: 2hwk

Contents

Protein chain

320 a.a. *

Ligands

FMT ×3

Waters ×25

* Residue conservation analysis

PDB id:

2hwk

Name:

Hydrolase

Title:

Crystal structure of venezuelan equine encephalitis alphavirus nsp2 protease domain

Structure:

Helicase nsp2. Chain: a. Fragment: nsp2pro. Synonym: protease, triphosphatase, ntpase. Engineered: yes

Source:

Venezuelan equine encephalitis virus (strain tc-83). Organism_taxid: 11037. Strain: tc-83. Gene: ns. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.45Å R-factor: 0.192 R-free: 0.242

Authors:

A.T.Russo,M.A.White,S.J.Watowich

Key ref:

A.T.Russo et al. (2006). The crystal structure of the Venezuelan equine encephalitis alphavirus nsP2 protease. Structure, 14, 1449-1458. PubMed id: 16962975 DOI: 10.1016/j.str.2006.07.010

Date:

01-Aug-06 Release date: 26-Sep-06

Protein chain

Q9WIJ1  (Q9WIJ1_EEVVT) -  Putative nonstructural polyprotein from Venezuelan equine encephalitis virus (strain Trinidad donkey)

Seq: 1879 a.a.

Struc: 320 a.a.

Enzyme reactions

• Enzyme class: E.C.3.6.1.15 - nucleoside-triphosphate phosphatase.
• Reaction: a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + phosphate + H⁺

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

Key reference

DOI no: 10.1016/j.str.2006.07.010

Structure 14:1449-1458 (2006)

PubMed id: 16962975

The crystal structure of the Venezuelan equine encephalitis alphavirus nsP2 protease.

A.T.Russo, M.A.White, S.J.Watowich.

ABSTRACT

Alphavirus replication and propagation is dependent on the protease activity of the viral nsP2 protein, which cleaves the nsP1234 polyprotein replication complex into functional components. Thus, nsP2 is an attractive target for drug discovery efforts to combat highly pathogenic alphaviruses. Unfortunately, antiviral development has been hampered by a lack of structural information for the nsP2 protease. Here, we report the crystal structure of the nsP2 protease (nsP2pro) from Venezuelan equine encephalitis alphavirus determined at 2.45 A resolution. The protease structure consists of two distinct domains. The nsP2pro N-terminal domain contains the catalytic dyad cysteine and histidine residues organized in a protein fold that differs significantly from any known cysteine protease or protein folds. The nsP2pro C-terminal domain displays structural similarity to S-adenosyl-L-methionine-dependent RNA methyltransferases and provides essential elements that contribute to substrate recognition and may also regulate the structure of the substrate binding cleft.

Selected figure(s)

Figure 3.
Figure 3. Superposition of the nsP2pro Catalytic Dyad with Those of Papain and Human Cathepsin X
(A) A close-up view of the catalytic dyad of cathepsin X (green) and papain (red) showing strong similarity between the two and clear structural differences from VEEV nsP2pro (light blue). The divergence of nsP2pro from the papain and cathepsin X structures increases with increasing distance from catalytic dyad.
(B) An expanded view of the superposition of cysteine protease structures shows that cathepsin X (green) and papain (red) have similar two-domain tertiary structures, and that they form distinct tertiary structures relative to VEEV nsP2pro (light blue).

Figure 6.
Figure 6. Locations of Temperature-Sensitive Mutants Mapped onto the VEEV nsP2pro Structure
The nsP2pro cartoon is colored by domain as in Figure 2. Stick representations of residues are colored by atom type, with carbon atoms in the mutation sites (labeled) colored green and the catalytic dyad (unlabeled) colored magenta.

The above figures are reprinted by permission from Cell Press: Structure (2006, 14, 1449-1458) copyright 2006.

Figures were selected by an automated process.