DB code: D00869

RLCP classification 3.676.249900.37 : Transfer
CATH domain 3.40.30.10 : Glutaredoxin Catalytic domain
3.40.30.10 : Glutaredoxin Catalytic domain
E.C. 1.11.1.15
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.40.30.10 : Glutaredoxin S00916 S00279 M00184 D00866 D00870 D00278

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P44758 Hybrid peroxiredoxin hyPrx5
EC 1.11.1.15
Thioredoxin reductase
NP_438729.1 (Protein)
NC_000907.1 (DNA/RNA sequence)
PF00462 (Glutaredoxin)
PF08534 (Redoxin)
[Graphical View]

KEGG enzyme name
Peroxiredoxin
Thioredoxin peroxidase
Tryparedoxin peroxidase
Alkyl hydroperoxide reductase C22
AhpC
TrxPx
TXNPx
Prx
PRDX

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P44758 PRX5_HAEIN 2 R'-SH + ROOH = R'-S-S-R' + H(2)O + ROH. Homotetramer.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C16736 C15498 C15496 C00001 C01335 I00142 I00143
E.C.
Compound R'-SH ROOH R'-S-S-R' H2O ROH Peptidyl-Cys-sulfenic acid Transient disulfide bond between peptidyl-Cys
Type sulfhydryl group others disulfide bond H2O carbohydrate
ChEBI 15377
PubChem 22247451
962
1nm3A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1nm3B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1nm3A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:CYS_180-CYS_183 Unbound Unbound Unbound
1nm3B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:CYS_180-CYS_183 Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Literature [1], [2], [3], [4], [6], [7]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1nm3A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain THR 46;CYS 49;ARG 126 GLY 43;THR 48;CYS 49
1nm3B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain THR 46;CYS 49;ARG 126 GLY 43;THR 48;CYS 49
1nm3A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 180;CYS 183
1nm3B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 180;CYS 183

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
Fig. 1
[4]
Figure 2, Figure 3
[5]
Fig. 7
[6]
Fig. 8
[8]
Scheme 2

References
[1]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
Medline ID
PubMed ID 12529327
Journal J Biol Chem
Year 2003
Volume 278
Pages 10790-8
Authors Kim SJ, Woo JR, Hwang YS, Jeong DG, Shin DH, Kim K, Ryu SE
Title The tetrameric structure of Haemophilus influenza hybrid Prx5 reveals interactions between electron donor and acceptor proteins.
Related PDB 1nm3
Related UniProtKB P44758
[2]
Resource
Comments
Medline ID
PubMed ID 12517450
Journal Trends Biochem Sci
Year 2003
Volume 28
Pages 32-40
Authors Wood ZA, Schroder E, Robin Harris J, Poole LB
Title Structure, mechanism and regulation of peroxiredoxins.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 18084889
Journal Subcell Biochem
Year 2007
Volume 44
Pages 41-60
Authors Karplus PA, Hall A
Title Structural survey of the peroxiredoxins.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 18084890
Journal Subcell Biochem
Year 2007
Volume 44
Pages 61-81
Authors Poole LB
Title The catalytic mechanism of peroxiredoxins.
Related PDB
Related UniProtKB
[5]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.47 ANGSTROMS).
Medline ID
PubMed ID 19477183
Journal J Mol Biol
Year 2009
Volume 390
Pages 951-66
Authors Liao SJ, Yang CY, Chin KH, Wang AH, Chou SH
Title Insights into the alkyl peroxide reduction pathway of Xanthomonas campestris bacterioferritin comigratory protein from the trapped intermediate-ligand complex structures.
Related PDB 3gkk 3gkm 3gkn
Related UniProtKB Q8P9V9
[6]
Resource
Comments
Medline ID
PubMed ID 20643143
Journal J Mol Biol
Year 2010
Volume 402
Pages 194-209
Authors Hall A, Parsonage D, Poole LB, Karplus PA
Title Structural evidence that peroxiredoxin catalytic power is based on transition-state stabilization.
Related PDB 3mng
Related UniProtKB P30044
[7]
Resource
Comments
Medline ID
PubMed ID 20969484
Journal Antioxid Redox Signal
Year 2011
Volume 15
Pages 795-815
Authors Hall A, Nelson K, Poole LB, Karplus PA
Title Structure-based insights into the catalytic power and conformational dexterity of peroxiredoxins.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 21391663
Journal Chem Res Toxicol
Year 2011
Volume 24
Pages 434-50
Authors Ferrer-Sueta G, Manta B, Botti H, Radi R, Trujillo M, Denicola A
Title Factors affecting protein thiol reactivity and specificity in peroxide reduction.
Related PDB
Related UniProtKB

Comments
Peroxiredoxins (Prxs) can be classified into three categories (see [2]):
(1) typical 2-Cys Prxs; conservation of two redox-active cysteines; homodimers having two identical active sites.
(2) atypical 2-Cys Prxs; conservation of two redox-active cysteines; functionally monomeric.
(3) 1-Cys Prxs; only one cysteine.
This enzyme belongs to the category of 1-Cys Prxs.
The redox-active cysteine is referred to as the peroxidatic cysteine, in contrast to the second cysteine, the resolving cysteine, in the 2-Cys Prxs.
Moreover, this enzyme has a glutaredoxin (Grx) domain in the C-terminus, which contains two cysteine residues (Cys180 and Cys 183) that can act as an electron donor for the Prx domain.
According to the literature [1], oxidized C-terminal Grx domain can be reduced by reduced glutathione (GSH). Cys180 can form a disulfide bond with the cysteine residue of GSH.
Thus, this enzyme catalyzes the following reactions (see [1], [2], [6], [8]):
(A) Transfer of peroxide oxygen from another peroxide oxygen to the peroxidatic Cys, forming Cys-sulfenate (I00142):
(A0) Sidechains of Thr46 and Arg126 may lower the pKa of sidechain of Cys49, along with the mainchain amide groups of Gly43 and Cys49.
(A1) The thiolate of Cys49 makes a nucleophilic (in-line) attack on the electrophilic oxygen atom of hydroperoxide, leading to the transition-state (SN2-like reaction).
(A2) During the transition-state, sidechains of Arg126 and Thr46 stabilize the transferred oxygen atom, whereas the acceptor, thiolate of Cys49, is stabilized by sidechains of Arg126 and Thr46, and mainchain amide of Cys49. Moreover, the leaving alkoxide (RO-) is stabilized by mainchain amide of Thr48.
(A3) Finally, the bond cleavage and new bond formation complete, forming an sulfenic acid intermediate (I00142).
(B) Transfer of sulfur atom of the peroxidatic Cys from the hydroxyl group to Cys180 of Grx domain, releasing H2O and forming a disulfide bond (I00143):
(B1) Cys180 makes a nucleophilic attack on the sulfur atom of Cys49, relasing OH group. This reaction forms a new disulfide bond between Cys49 and Cys180. However, it is not clear how Cys180 can be activated for the nucleophilicity, and whether a protonation to leaving OH group occurs.
(C) Electron transfer from Cys183 of Grx domain to the disulfide bond (thiol-disulfide exchange):
(C1) Cys183 makes a nucleophilic attack on the sulfur atom of Cys180, relasing Cys49. This reaction forms a new disulfide bond between Cys180 and Cys183. However, it is not clear how Cys183 can be activated for the nucleophilicity.

Created Updated
2012-07-17 2012-09-07