Q7BHK8 (AHPC_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Alkyl hydroperoxide reductase subunit C
Short name=MtAhpC
EC=1.11.1.15

Alternative name(s):
Peroxiredoxin
Thioredoxin peroxidase

Gene names

Name:	ahpC
Ordered Locus Names:	Rv2428, MT2503

Organism

Mycobacterium tuberculosis

Taxonomic identifier

1773 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	195 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Does not however seem to play a role in detoxification of isoniazid. Ref.7 Ref.9 Ref.10
Catalytic activity	2 R'-SH + ROOH = R'-S-S-R' + H2O + ROH.
Subunit structure	Homodimer; disulfide-linked, upon oxidation. It has been shown to form 10-mers. The crystal structure of Ser-176 implies that the reduced protein may form a 10- or 12-mer during the catalytic cycle. Identified in a complex with AhpD, DltA and Lpd. Ref.9 Ref.10 Ref.12
Induction	Induced in isoniazid (INH)-resistant, KatG-deficient strains as well as in INH-sensitive strains when challenged with the drug. Increased expression in these strains probably compensates for loss of katG activity in detoxification of organic peroxides. A possible member of the dormancy regulon. Induced in response to reduced oxygen tension (hypoxia). It is hoped that this regulon will give insight into the latent, or dormant phase of infection. Ref.6 Ref.8
Post-translational modification	The Cys-61-SH group is the primary site of oxidation by H2O2, and the oxidized Cys-61 (probably Cys-SOH) rapidly reacts with Cys-174-SH of the other subunit to form an intermolecular disulfide. This disulfide is subsequently reduced by thioredoxin Probable.
Miscellaneous	In the absence of both Cys-174 and Cys-176 the enzyme may adopt a 1-Cys Prx-type mechanism, which would account for the apparent suppression of the Ala-174 mutation by Ala-176.
Sequence similarities	Belongs to the AhpC/TSA family. Contains 1 thioredoxin domain.
Biophysicochemical properties	Kinetic parameters: KM=5.38 mM for t-butyl hydroperoxide Ref.9

Ontologies

Keywords
Biological process	Stress response
Domain	Redox-active center
Molecular function	Antioxidant Oxidoreductase Peroxidase
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	cell redox homeostasis Inferred from direct assay Ref.10. Source: MTBBASE protein homooligomerization Inferred from physical interaction Ref.7Ref.12. Source: MTBBASE response to nitrosative stress Inferred from mutant phenotype. Source: MTBBASE
Cellular component	plasma membrane Inferred from direct assay. Source: MTBBASE
Molecular function	alkyl hydroperoxide reductase activity Inferred from direct assay. Source: MTBBASE hydroperoxide reductase activity Inferred from direct assay Ref.7. Source: MTBBASE peroxidase activity Inferred from direct assay Ref.10. Source: MTBBASE peroxiredoxin activity Inferred from direct assay. Source: MTBBASE protein binding Inferred from physical interaction Ref.11. Source: MTBBASE
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.6

Chain

2 – 195

194

Alkyl hydroperoxide reductase subunit C

PRO_0000392913

Regions

Domain

4 – 170

167

Thioredoxin

Sites

Active site

61

1

Cysteine sulfenic acid (-SOH) intermediate Probable

Amino acid modifications

Disulfide bond

61

Interchain (with C-174); in linked form

Disulfide bond

174

Interchain (with C-61); in linked form

Experimental info

Mutagenesis

61

1

C → A or S: No enzyme activity. Ref.7 Ref.9 Ref.11

Mutagenesis

174 – 176

3

CAC → AAA: 50% reduction in oxidation activity of dithiothreitol and 60% reduction in oxidation of thiocyanate. Ref.7 Ref.9 Ref.11

Mutagenesis

174

1

C → A: Very poor oxidation activity of dithiothreitol and thiocyanate. Ref.7 Ref.9 Ref.11

Mutagenesis

174

1

C → S in reconstituted in vitro system retains no enzyme activity. Ref.7 Ref.9 Ref.11

Mutagenesis

176

1

C → A: 50% reduction in oxidation activity of dithiothreitol and thiocyanate. Ref.7 Ref.9 Ref.11

Mutagenesis

176

1

C → S: Retains about 10% activity with tert-butylhydroperoxide. In reconstituted in vitro system retains 30% enzyme activity. Ref.7 Ref.9 Ref.11

Secondary structure

1

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195

Helix Strand Turn

Details...

Beta strand

14 – 18

5

Helix

23 – 25

3

Beta strand

35 – 39

5

Beta strand

47 – 52

6

Helix

62 – 70

9

Helix

72 – 76

5

Turn

77 – 79

3

Beta strand

80 – 83

4

Beta strand

86 – 88

3

Helix

90 – 99

10

Helix

103 – 105

3

Beta strand

110 – 112

3

Helix

117 – 121

5

Beta strand

133 – 138

6

Beta strand

142 – 150

9

Helix

158 – 169

12

Sequences

	Sequence		Length	Mass (Da)
	Q7BHK8 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: 011C1014F07C7095	FASTA	195	21,566
	10 20 30 40 50 60 MPLLTIGDQF PAYQLTALIG GDLSKVDAKQ PGDYFTTITS DEHPGKWRVV FFWPKDFTFV 70 80 90 100 110 120 CPTEIAAFSK LNDEFEDRDA QILGVSIDSE FAHFQWRAQH NDLKTLPFPM LSDIKRELSQ 130 140 150 160 170 180 AAGVLNADGV ADRVTFIVDP NNEIQFVSAT AGSVGRNVDE VLRVLDALQS DELCACNWRK 190 GDPTLDAGEL LKASA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Disparate responses to oxidative stress in saprophytic and pathogenic mycobacteria." Sherman D.R., Sabo P.J., Hickey M.J., Arain T.M., Mahairas G.G., Yuan Y., Barry C.E. III, Stover C.K. Proc. Natl. Acad. Sci. U.S.A. 92:6625-6629(1995) [PubMed: 7604044] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Mycobacterium tuberculosis is a natural mutant with an inactivated oxidative-stress regulatory gene: implications for sensitivity to isoniazid." Deretic V., Philipp W., Dhandayuthapani S., Mudd M.H., Curcic R., Garbe T., Heym B., Via L.E., Cole S.T. Mol. Microbiol. 17:889-900(1995) [PubMed: 8596438] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 25618 / H37Rv.
[3]	"Mutation associated with isoniazid resistance in Italian isolates of Mycobacterium tuberculosis." Orru G., Iona E., Memmi G., Oggioni M.R., Fattorini L., Orefici G., Pozzi G. Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: An01, F07, Rm23, Rm24 and Rm30.
[4]	"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.
[5]	"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.
[6]	"Compensatory ahpC gene expression in isoniazid-resistant Mycobacterium tuberculosis." Sherman D.R., Mdluli K., Hickey M.J., Arain T.M., Morris S.L., Barry C.E. III, Stover C.K. Science 272:1641-1643(1996) [PubMed: 8658136] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-16, LACK OF ACTION ON ISONIAZID, INDUCTION IN DRUG-RESISTANT BACTERIA. Strain: ATCC 35822.
[7]	"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, MUTAGENESIS OF CYS-61; CYS-174 AND CYS-176.
[8]	"Regulation of the Mycobacterium tuberculosis hypoxic response gene encoding alpha -crystallin." Sherman D.R., Voskuil M., Schnappinger D., Liao R., Harrell M.I., Schoolnik G.K. Proc. Natl. Acad. Sci. U.S.A. 98:7534-7539(2001) [PubMed: 11416222] [Abstract] Cited for: INDUCTION BY HYPOXIA. Strain: ATCC 25618 / H37Rv.
[9]	"Site-directed mutagenesis reveals a novel catalytic mechanism of Mycobacterium tuberculosis alkylhydroperoxidase C." Chauhan R., Mande S.C. Biochem. J. 367:255-261(2002) [PubMed: 12084012] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, FUNCTION AS ANTIOXIDANT, MUTAGENESIS OF CYS-61; CYS-174; CYS-176 AND 174-CYS--CYS-176.
[10]	"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: FUNCTION, SUBUNIT. Strain: ATCC 25618 / H37Rv.
[11]	"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: MUTAGENESIS OF CYS-61; CYS-174 AND CYS-176.
[12]	"Structure and mechanism of the alkyl hydroperoxidase AhpC, a key element of the Mycobacterium tuberculosis defense system against oxidative stress." Guimaraes B.G., Souchon H., Honore N., Saint-Joanis B., Brosch R., Shepard W., Cole S.T., Alzari P.M. J. Biol. Chem. 280:25735-25742(2005) [PubMed: 15886207] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF MUTANT SER-176, POSSIBLE CATALYTIC MECHANISM, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U18264 Genomic DNA. Translation: AAA79919.1.
U16243 Genomic DNA. Translation: AAC43585.1.
AF313459 Genomic DNA. Translation: AAG34172.1.
AF313460 Genomic DNA. Translation: AAG34173.1.
AF313461 Genomic DNA. Translation: AAG34174.1.
AF313462 Genomic DNA. Translation: AAG34175.1.
AF313463 Genomic DNA. Translation: AAG34176.1.
BX842579 Genomic DNA. Translation: CAB03768.1.
AE000516 Genomic DNA. Translation: AAK46800.1.

RefSeq

NP_216944.1. NC_000962.2.
NP_336986.1. NC_002755.2.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2BMX	X-ray	2.40	A/B/C	1-195	[»]

ProteinModelPortal

Q7BHK8.

SMR

Q7BHK8. Positions 2-170.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

EBMYCT00000003061; EBMYCP00000003061; EBMYCG00000003059.
EBMYCT00000072680; EBMYCP00000070739; EBMYCG00000072675.

GeneID

885717.
925827.

GenomeReviews

Gene locus MT2503 in contig AE000516_GR.
Gene locus Rv2428 in contig AL123456_GR.

KEGG

mtc:MT2503.
mtu:Rv2428.

PATRIC

18127254. VBIMycTub22151_2735.

TIGR

MT2503.

Organism-specific databases

TubercuList

Rv2428.

Phylogenomic databases

GeneTree

EBGT00050000015905.

HOGENOM

HBG493509.

OMA

PFPMLAD.

PhylomeDB

Q7BHK8.

ProtClustDB

CLSK791845.

Family and domain databases

InterPro

IPR000866. AhpC/TSA.
IPR024706. Peroxiredoxin_AhpC-typ.
IPR012336. Thioredoxin-like_fold.
[Graphical view]

Gene3D

G3DSA:3.40.30.10. Thioredoxin_fold. 1 hit.

KO

K03386.

Pfam

PF00578. AhpC-TSA. 1 hit.
[Graphical view]

PIRSF

PIRSF000239. AHPC. 1 hit.

SUPFAM

SSF52833. Thiordxn-like_fd. 1 hit.

PROSITE

PS00194. THIOREDOXIN_1. False negative.
PS51352. THIOREDOXIN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

AHPC_MYCTU

Accession

Primary (citable) accession number: Q7BHK8
Secondary accession number(s): Q79FE2, Q7D758

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 23, 2010
Last sequence update:	July 5, 2004
Last modified:	January 25, 2012
This is version 70 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program