EzCatDB: D00869
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DB codeD00869
RLCP classification3.676.249900.37 : Transfer
CATH domainDomain 13.40.30.10 : GlutaredoxinCatalytic domain
Domain 23.40.30.10 : GlutaredoxinCatalytic domain
E.C.1.11.1.15

CATH domainRelated DB codes (homologues)
3.40.30.10 : GlutaredoxinS00916,S00279,M00184,D00866,D00870,D00278

Enzyme Name
UniProtKBKEGG

P44758
Protein nameHybrid peroxiredoxin hyPrx5Peroxiredoxin
Thioredoxin peroxidase
Tryparedoxin peroxidase
Alkyl hydroperoxide reductase C22
AhpC
TrxPx
TXNPx
Prx
PRDX
SynonymsEC 1.11.1.15
Thioredoxin reductase
RefSeqNP_438729.1 (Protein)
NC_000907.1 (DNA/RNA sequence)
PfamPF00462 (Glutaredoxin)
PF08534 (Redoxin)
[Graphical view]


UniProtKB:Accession NumberP44758
Entry namePRX5_HAEIN
Activity2 R'-SH + ROOH = R'-S-S-R' + H(2)O + ROH.
SubunitHomotetramer.
Subcellular location
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC16736C15498C15496C00001C01335I00142I00143
CompoundR'-SHROOHR'-S-S-R'H2OROHPeptidyl-Cys-sulfenic acidTransient disulfide bond between peptidyl-Cys
Typesulfhydryl groupothersdisulfide bondH2Ocarbohydrate

ChEBI


15377



PubChem


962
22247451



               
1nm3A01UnboundUnboundUnbound UnboundUnboundUnbound
1nm3B01UnboundUnboundUnbound UnboundUnboundUnbound
1nm3A02UnboundUnboundBound:CYS 180-CYS 183 UnboundUnboundUnbound
1nm3B02UnboundUnboundBound:CYS 180-CYS 183 UnboundUnboundUnbound

Active-site residues
resource
Literature [1], [2], [3], [4], [6], [7]
pdbCatalytic residuesMain-chain involved in catalysis
          
1nm3A01THR  46;CYS  49;ARG 126
GLY  43;THR  48;CYS  49
1nm3B01THR  46;CYS  49;ARG 126
GLY  43;THR  48;CYS  49
1nm3A02CYS 180;CYS 183
 
1nm3B02CYS 180;CYS 183
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]Fig. 1
[4]Figure 2, Figure 3
[5]Fig. 7
[6]Fig. 8
[8]Scheme 2

references
[1]
CommentsX-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
PubMed ID12529327
JournalJ Biol Chem
Year2003
Volume278
Pages10790-8
AuthorsKim SJ, Woo JR, Hwang YS, Jeong DG, Shin DH, Kim K, Ryu SE
TitleThe tetrameric structure of Haemophilus influenza hybrid Prx5 reveals interactions between electron donor and acceptor proteins.
Related PDB1nm3
Related UniProtKBP44758
[2]
PubMed ID12517450
JournalTrends Biochem Sci
Year2003
Volume28
Pages32-40
AuthorsWood ZA, Schroder E, Robin Harris J, Poole LB
TitleStructure, mechanism and regulation of peroxiredoxins.
[3]
PubMed ID18084889
JournalSubcell Biochem
Year2007
Volume44
Pages41-60
AuthorsKarplus PA, Hall A
TitleStructural survey of the peroxiredoxins.
[4]
PubMed ID18084890
JournalSubcell Biochem
Year2007
Volume44
Pages61-81
AuthorsPoole LB
TitleThe catalytic mechanism of peroxiredoxins.
[5]
CommentsX-RAY CRYSTALLOGRAPHY (1.47 ANGSTROMS).
PubMed ID19477183
JournalJ Mol Biol
Year2009
Volume390
Pages951-66
AuthorsLiao SJ, Yang CY, Chin KH, Wang AH, Chou SH
TitleInsights into the alkyl peroxide reduction pathway of Xanthomonas campestris bacterioferritin comigratory protein from the trapped intermediate-ligand complex structures.
Related PDB3gkk,3gkm,3gkn
Related UniProtKBQ8P9V9
[6]
PubMed ID20643143
JournalJ Mol Biol
Year2010
Volume402
Pages194-209
AuthorsHall A, Parsonage D, Poole LB, Karplus PA
TitleStructural evidence that peroxiredoxin catalytic power is based on transition-state stabilization.
Related PDB3mng
Related UniProtKBP30044
[7]
PubMed ID20969484
JournalAntioxid Redox Signal
Year2011
Volume15
Pages795-815
AuthorsHall A, Nelson K, Poole LB, Karplus PA
TitleStructure-based insights into the catalytic power and conformational dexterity of peroxiredoxins.
[8]
PubMed ID21391663
JournalChem Res Toxicol
Year2011
Volume24
Pages434-50
AuthorsFerrer-Sueta G, Manta B, Botti H, Radi R, Trujillo M, Denicola A
TitleFactors affecting protein thiol reactivity and specificity in peroxide reduction.

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.

createdupdated
2012-07-172012-09-07


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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