PDBsum entry 2e2m

Oxidoreductase

PDB id: 2e2m

Contents

Protein chains

(+ 4 more) 236 a.a. *

Waters ×422

* Residue conservation analysis

PDB id:

2e2m

Name:

Oxidoreductase

Title:

Crystal structure of archaeal peroxiredoxin, thioredoxin peroxidase from aeropyrum pernix k1 (sulfinic acid form)

Structure:

Probable peroxiredoxin. Chain: a, b, c, d, e, f, g, h, i, j. Synonym: thioredoxin peroxidase. Engineered: yes. Mutation: yes

Source:

Aeropyrum pernix. Organism_taxid: 272557. Strain: k1. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.60Å R-factor: 0.234 R-free: 0.280

Authors:

T.Nakamura,T.Yamamoto,M.Abe,H.Matsumura,Y.Hagihara,T.Goto, T.Yamaguchi,T.Inoue

Key ref:

T.Nakamura et al. (2008). Oxidation of archaeal peroxiredoxin involves a hypervalent sulfur intermediate. Proc Natl Acad Sci U S A, 105, 6238-6242. PubMed id: 18436649 DOI: 10.1073/pnas.0709822105

Date:

14-Nov-06 Release date: 20-Nov-07

Protein chains

Q9Y9L0  (TDXH_AERPE) -  Peroxiredoxin from Aeropyrum pernix (strain ATCC 700893 / DSM 11879 / JCM 9820 / NBRC 100138 / K1)

Seq: 250 a.a.

Struc: 236 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

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: 10.1073/pnas.0709822105

Proc Natl Acad Sci U S A 105:6238-6242 (2008)

PubMed id: 18436649

Oxidation of archaeal peroxiredoxin involves a hypervalent sulfur intermediate.

T.Nakamura, T.Yamamoto, M.Abe, H.Matsumura, Y.Hagihara, T.Goto, T.Yamaguchi, T.Inoue.

ABSTRACT

The oxidation of thiol groups in proteins is a common event in biochemical processes involving disulfide bond formation and in response to an increased level of reactive oxygen species. It has been widely accepted that the oxidation of a cysteine side chain is initiated by the formation of cysteine sulfenic acid (Cys-SOH). Here, we demonstrate a mechanism of thiol oxidation through a hypervalent sulfur intermediate by presenting crystallographic evidence from an archaeal peroxiredoxin (Prx), the thioredoxin peroxidase from Aeropyrum pernix K1 (ApTPx). The reaction of Prx, which is the reduction of a peroxide, depends on the redox active cysteine side chains. Oxidation by hydrogen peroxide converted the active site peroxidatic Cys-50 of ApTPx to a cysteine sulfenic acid derivative, followed by further oxidation to cysteine sulfinic and sulfonic acids. The crystal structure of the cysteine sulfenic acid derivative was refined to 1.77 A resolution with R(cryst) and R(free) values of 18.8% and 22.0%, respectively. The refined structure, together with quantum chemical calculations, revealed that the sulfenic acid derivative is a type of sulfurane, a hypervalent sulfur compound, and that the S(gamma) atom is covalently linked to the N(delta1) atom of the neighboring His-42. The reaction mechanism is revealed by the hydrogen bond network around the peroxidatic cysteine and the motion of the flexible loop covering the active site and by quantum chemical calculations. This study provides evidence that a hypervalent sulfur compound occupies an important position in biochemical processes.

Selected figure(s)

Figure 3.
Interaction of the hypervalent intermediate with surrounding residues.

Figure 4.
Structural change and putative reaction scheme of ApTPx. (a–c) Close-ups around the peroxidatic cysteine residues of the reduced, preoxidation, and hypervalent sulfur forms, respectively. (d) Superimposition of the reduced (green) and hypervalent sulfur (purple) forms. Proposed reaction scheme of ApTPx is shown in e. Cso represents the C[p] residue in the hypervalent sulfur form.

Figures were selected by an automated process.