P0A5N4 (AHPD_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Alkyl hydroperoxide reductase AhpD
EC=1.11.1.15

Alternative name(s):
Alkylhydroperoxidase AhpD

Gene names

Name:	ahpD
Ordered Locus Names:	Rv2429, MT2504
ORF Names:	MTCY428.17c

Organism

Mycobacterium tuberculosis

Taxonomic identifier

1773 [NCBI]

Taxonomic lineage

Bacteria › Actinobacteria › Actinobacteridae › Actinomycetales › Corynebacterineae › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex

Protein attributes

Sequence length	177 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Antioxidant protein with alkyl hydroperoxidase activity. Required for the reduction of the AhpC active site cysteine residues and for the regeneration of the AhpC enzyme activity. Ref.4 Ref.7 Ref.8 Together with AhpD, DltA and Lpd constitutes an NADH-dependent peroxidase active against hydrogen and alkyl peroxides as well as serving as a peroxynitrite reductase, thus protecting the bacterium against reactive nitrogen intermediates and oxidative stress generated by the host immune system. Ref.4 Ref.7 Ref.8
Catalytic activity	2 R'-SH + ROOH = R'-S-S-R' + H2O + ROH. HAMAP MF_01676
Subunit structure	Homotrimer. Identified in a complex with AhpC and Lpd. Ref.4 Ref.5 Ref.6 Ref.7
Sequence similarities	Belongs to the AhpD family.
Biophysicochemical properties	pH dependence: Optimum pH is 7.2. Ref.8

Ontologies

Keywords
Domain	Redox-active center
Molecular function	Antioxidant Oxidoreductase Peroxidase
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell redox homeostasis Inferred from physical interaction Ref.7. Source: MTBBASE protein homotrimerization Inferred from physical interaction Ref.7. Source: MTBBASE
Cellular component	plasma membrane Inferred from direct assay. Source: MTBBASE
Molecular function	disulfide oxidoreductase activity Inferred from direct assay Ref.7. Source: MTBBASE hydroperoxide reductase activity Inferred from direct assay Ref.4. Source: MTBBASE peroxidase activity Inferred from electronic annotation. Source: UniProtKB-KW peroxiredoxin activity Inferred from electronic annotation. Source: EC protein homodimerization activity Inferred from physical interaction Ref.4. Source: MTBBASE
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 177

177

Alkyl hydroperoxide reductase AhpD HAMAP MF_01676

PRO_0000064507

Sites

Active site

130

1

Proton donor Ref.6

Active site

133

1

Cysteine sulfenic acid (-SOH) intermediate Ref.6

Amino acid modifications

Disulfide bond

130 ↔ 133

Alternate Ref.5

Disulfide bond

133

Interchain (with C-61 in AhpC); in linked form Ref.5

Experimental info

Mutagenesis

118

1

E → Q: Reduces protein stability. No effect on catalytic activity. Ref.8

Mutagenesis

130

1

C → S: Loss of activity. Ref.4 Ref.7 Ref.8

Mutagenesis

132

1

H → F: Slightly reduced catalytic activity. Ref.8

Mutagenesis

132

1

H → Q: Slightly reduced catalytic activity. Ref.8

Mutagenesis

133

1

C → S: Loss of activity. Loss of interchain disulfide bond with AhpC. Ref.4 Ref.7 Ref.8

Mutagenesis

137

1

H → F: Reduced catalytic activity. Ref.8

Mutagenesis

137

1

H → Q: Slightly reduced catalytic activity. Ref.8

Secondary structure

1

.

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177

Helix Strand Turn

Details...

Helix

5 – 9

5

Helix

12 – 14

3

Helix

15 – 25

11

Beta strand

28 – 30

3

Helix

32 – 45

14

Helix

49 – 59

11

Turn

60 – 62

3

Helix

65 – 90

26

Turn

91 – 97

7

Helix

105 – 108

4

Helix

114 – 128

15

Helix

131 – 143

13

Helix

148 – 174

27

Sequences

	Sequence		Length	Mass (Da)
	P0A5N4 [UniParc]. Last modified March 15, 2005. Version 1. Checksum: B7DD28AA9BD9B24C	FASTA	177	18,781
	10 20 30 40 50 60 MSIEKLKAAL PEYAKDIKLN LSSITRSSVL DQEQLWGTLL ASAAATRNPQ VLADIGAEAT 70 80 90 100 110 120 DHLSAAARHA ALGAAAIMGM NNVFYRGRGF LEGRYDDLRP GLRMNIIANP GIPKANFELW 130 140 150 160 170 SFAVSAINGC SHCLVAHEHT LRTVGVDREA IFEALKAAAI VSGVAQALAT IEALSPS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Zhang Y., Dhandayuthapani S., Deretic V. Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 25618 / H37Rv.
[2]	"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence." Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E., Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K. , Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K., Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J., Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S., Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S., Barrell B.G. Nature 393:537-544(1998) [PubMed: 9634230] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 25618 / H37Rv.
[3]	"Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains." Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O., Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K., Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L., Delcher A., Utterback T.R. , Weidman J.F., Khouri H.M., Gill J., Mikula A., Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M. J. Bacteriol. 184:5479-5490(2002) [PubMed: 12218036] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: CDC 1551 / Oshkosh.
[4]	"The AhpC and AhpD antioxidant defense system of Mycobacterium tuberculosis." Hillas P.J., del Alba F.S., Oyarzabal J., Wilks A., Ortiz De Montellano P.R. J. Biol. Chem. 275:18801-18809(2000) [PubMed: 10766746] [Abstract] Cited for: FUNCTION, SUBUNIT, MUTAGENESIS OF CYS-130 AND CYS-133.
[5]	"Intermolecular interactions in the AhpC/AhpD antioxidant defense system of Mycobacterium tuberculosis." Koshkin A., Knudsen G.M., Ortiz De Montellano P.R. Arch. Biochem. Biophys. 427:41-47(2004) [PubMed: 15178486] [Abstract] Cited for: SUBUNIT, DISULFIDE BONDS.
[6]	"The crystal structure of Mycobacterium tuberculosis alkylhydroperoxidase AhpD, a potential target for antitubercular drug design." Nunn C.M., Djordjevic S., Hillas P.J., Nishida C.R., Ortiz de Montellano P.R. J. Biol. Chem. 277:20033-20040(2002) [PubMed: 11914371] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS), ACTIVE SITE, SUBUNIT.
[7]	"Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein." Bryk R., Lima C.D., Erdjument-Bromage H., Tempst P., Nathan C. Science 295:1073-1077(2002) [PubMed: 11799204] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), FUNCTION, SUBUNIT, MUTAGENESIS OF CYS-130 AND CYS-133. Strain: ATCC 25618 / H37Rv.
[8]	"The mechanism of Mycobacterium tuberculosis alkylhydroperoxidase AhpD as defined by mutagenesis, crystallography, and kinetics." Koshkin A., Nunn C.M., Djordjevic S., Ortiz de Montellano P.R. J. Biol. Chem. 278:29502-29508(2003) [PubMed: 12761216] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF MUTANTS GLN-132 AND PHE-137, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF GLU-118; CYS-130; HIS-132; CYS-133 AND HIS-137.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U44840 Genomic DNA. Translation: AAA86657.1.
BX842579 Genomic DNA. Translation: CAB03767.1.
AE000516 Genomic DNA. Translation: AAK46801.1.

PIR

C70679.

RefSeq

NP_216945.1. NC_000962.2.
NP_336987.1. NC_002755.2.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1GU9	X-ray	1.90	A/B/C/D/E/F/G/H/I/J/K/L	1-177	[»]
1KNC	X-ray	2.00	A/B/C	1-177	[»]
1LW1	X-ray	2.30	A/B/C	1-177	[»]
1ME5	X-ray	2.40	A/B/C	1-177	[»]

ProteinModelPortal

P0A5N4.

SMR

P0A5N4. Positions 2-175.

ModBase

Search...

Protein family/group databases

PeroxiBase

4558. MtuAhpD.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

EBMYCT00000002260; EBMYCP00000002260; EBMYCG00000002258.
EBMYCT00000069420; EBMYCP00000067479; EBMYCG00000069415.

GeneID

885959.
925835.

GenomeReviews

Gene locus MT2504 in contig AE000516_GR.
Gene locus Rv2429 in contig AL123456_GR.

KEGG

mtc:MT2504.
mtu:Rv2429.

PATRIC

18127256. VBIMycTub22151_2736.

TIGR

MT2504.

Organism-specific databases

TubercuList

Rv2429.

Phylogenomic databases

GeneTree

EBGT00050000016698.

HOGENOM

HBG414634.

OMA

RAGLRMN.

ProtClustDB

CLSK791846.

Family and domain databases

HAMAP

MF_01676. AhpD.
[Tree]

InterPro

IPR004674. AhpD.
IPR004675. AhpD_core.
IPR003779. CMD.
[Graphical view]

KO

K04756.

Pfam

PF02627. CMD. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00777. AhpD. 1 hit.
TIGR00778. AhpD_dom. 1 hit.

ProtoNet

Search...

Entry information

Entry name

AHPD_MYCTU

Accession

Primary (citable) accession number: P0A5N4
Secondary accession number(s): Q57353

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	March 15, 2005
Last modified:	January 25, 2012
This is version 47 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program