PDBsum entry 1xvq

Oxidoreductase

PDB id: 1xvq

Contents

Protein chain

160 a.a. *

Ligands

NH4 ×2

Metals

YT3 ×3

Waters ×156

* Residue conservation analysis

PDB id:

1xvq

Name:

Oxidoreductase

Title:

Crystal structure of thiol peroxidase from mycobacterium tuberculosis

Structure:

Thiol peroxidase. Chain: a. Engineered: yes

Source:

Mycobacterium tuberculosis. Organism_taxid: 1773. Gene: tpx. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PQS)

Resolution:

1.75Å R-factor: 0.203 R-free: 0.225

Authors:

B.S.Rho,J.D.Pedelacq,L.W.Hung,J.M.Holton,D.Vigil,S.I.Kim,M.S.Park, T.C.Terwilliger,Tb Structural Genomics Consortium (Tbsgc)

Key ref:

B.S.Rho et al. (2006). Functional and structural characterization of a thiol peroxidase from Mycobacterium tuberculosis. J Mol Biol, 361, 850-863. PubMed id: 16884737 DOI: 10.1016/j.jmb.2006.05.076

Date:

28-Oct-04 Release date: 07-Dec-04

Protein chain

P9WG35  (TPX_MYCTU) -  Thiol peroxidase from Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)

Seq: 165 a.a.

Struc: 160 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.1.11.1.24 - thioredoxin-dependent peroxiredoxin.
• Reaction: a hydroperoxide + [thioredoxin]-dithiol = an alcohol + [thioredoxin]- disulfide + H2O

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

Added reference

DOI no: 10.1016/j.jmb.2006.05.076

J Mol Biol 361:850-863 (2006)

PubMed id: 16884737

Functional and structural characterization of a thiol peroxidase from Mycobacterium tuberculosis.

B.S.Rho, L.W.Hung, J.M.Holton, D.Vigil, S.I.Kim, M.S.Park, T.C.Terwilliger, J.D.Pédelacq.

ABSTRACT

A thiol peroxidase (Tpx) from Mycobacterium tuberculosis was functionally analyzed. The enzyme shows NADPH-linked peroxidase activity using a thioredoxin-thioredoxin reductase system as electron donor, and anti-oxidant activity in a thiol-dependent metal-catalyzed oxidation system. It reduces H2O2, t-butyl hydroperoxide, and cumene hydroperoxide, and is inhibited by sulfhydryl reagents. Mutational studies revealed that the peroxidatic (Cys60) and resolving (Cys93) cysteine residues are critical amino acids for catalytic activity. The X-ray structure determined to a resolution of 1.75 A shows a thioredoxin fold similar to that of other peroxiredoxin family members. Superposition with structural homologues in oxidized and reduced forms indicates that the M. tuberculosis Tpx is a member of the atypical two-Cys peroxiredoxin family. In addition, the short distance that separates the Calpha atoms of Cys60 and Cys93 and the location of these cysteine residues in unstructured regions may indicate that the M. tuberculosis enzyme is oxidized, though the side-chain of Cys60 is poorly visible. It is solely in the reduced Streptococcus pneumoniae Tpx structure that both residues are part of two distinct helical segments. The M. tuberculosis Tpx is dimeric both in solution and in the crystal structure. Amino acid residues from both monomers delineate the active site pocket.

Selected figure(s)

Figure 5.
Figure 5. The three-dimensional Mtb Tpx structure. (a) Stereo view of the 2F[o]−F[c] simulated-annealing omit map contoured at 0.75 σ level (blue) in the Cys60 and Cys93 region (yellow). The Cα trace of the reduced S. pneumoniae thiol peroxidase is shown in grey. Omitted residues correspond to Cys60, Cys80 and Cys93. (b) Stereo view of the Mtb Tpx structure. β-Strands are in green, α-helices in dark red, and 3[10] helix in cyan. Cys60, Cys80, and Cys93 are shown in ball-and-stick representation.

Figure 7.
Figure 7. Quaternary structure of the Mtb Tpx. (a) Dimer interface with residues making hydrogen bond contacts shown in ball-and-stick representation. (b) Overall shape and interface of dimer−dimer interactions. A rectangle indicates a close view of dimer−dimer interfaces. Dimers are shown in yellow (molecules A and B) and red (molecules C and D). Residues making close contacts interactions are shown with ball-and-stick representations. Hydrogen bonds are indicated by dotted lines.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2006, 361, 850-863) copyright 2006.

Figures were selected by an automated process.