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Q08129 (KATG_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Catalase-peroxidase

Short name=CP
EC=1.11.1.21
Alternative name(s):
Peroxidase/catalase
Gene names
Name:katG
Ordered Locus Names:Rv1908c, MT1959
ORF Names:MTCY180.10
OrganismMycobacterium tuberculosis [Reference proteome] [HAMAP]
Taxonomic identifier1773 [NCBI]
Taxonomic lineageBacteriaActinobacteriaActinobacteridaeActinomycetalesCorynebacterineaeMycobacteriaceaeMycobacteriumMycobacterium tuberculosis complex

Protein attributes

Sequence length740 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Bifunctional enzyme with both catalase and broad-spectrum peroxidase activity. Displays also NADH oxidase, isoniazid (INH) lyase and isonicotinoyl-NAD synthase activity. May play a role in the intracellular survival of mycobacteria. May be involved in DNA repair. Partly complements recA-deficient E.coli cells exposed to UV radiation, mitomycin C or hydrogen peroxide. Increases resistance to mitomycin C in E.coli cells deficient for either uvrA, uvrB or uvrC. Ref.9

Catalytic activity

Donor + H2O2 = oxidized donor + 2 H2O. HAMAP-Rule MF_01961

2 H2O2 = O2 + 2 H2O. HAMAP-Rule MF_01961

Cofactor

Binds 1 heme B (iron-protoporphyrin IX) group per subunit.

Subunit structure

Homodimer.

Induction

By treatment with H2O2. Repressed by FurA. Ref.10 Ref.11

Post-translational modification

The covalent Trp-Tyr-Met adduct is important for the catalase, but not the peroxidase activity of the enzyme By similarity. HAMAP-Rule MF_01961

Disruption phenotype

Cells show isoniazid (INH) resistance and are more sensitive to oxidative stress. Ref.7

Miscellaneous

In contrast to the Synechocystis sp. enzyme, no Trp radical is formed on the distal Trp residue (Trp-91). HAMAP-Rule MF_01961

The action of antitubercular drug isoniazid (INH) is dependent on its activation by KatG to form an isonicotinoyl-NAD adduct (IN-NAD). Resistance to INH can be due to mutations that reduces KatG activity. HAMAP-Rule MF_01961

Was identified as a high-confidence drug target. HAMAP-Rule MF_01961

Sequence similarities

Belongs to the peroxidase family. Peroxidase/catalase subfamily.

Biophysicochemical properties

Kinetic parameters:

KM=225 mM for H2O2 for the catalase reaction (at pH 5.5-6.0) Ref.15

KM=2.4 mM for H2O2 for the catalase reaction (at pH 7.0)

KM=360 µM for H2O2 for the peroxidase reaction

KM=67 µM for ABTS for the peroxidase reaction

Vmax=7620 µmol/min/mg enzyme for H2O2 for the catalase reaction (at pH 5.5-6.0)

Vmax=5700 µmol/min/mg enzyme for H2O2 for the catalase reaction (at pH 7.0)

Vmax=14 µmol/min/mg enzyme for ABTS for the peroxidase reaction

pH dependence:

Optimum pH is 4.75 for the peroxidase reaction.

Ontologies

Keywords
   Biological processAntibiotic resistance
Hydrogen peroxide
   LigandHeme
Iron
Metal-binding
   Molecular functionOxidoreductase
Peroxidase
   PTMOrganic radical
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processevasion or tolerance by symbiont of host-produced reactive oxygen species

Traceable author statement. Source: Reactome

hydrogen peroxide catabolic process

Inferred from direct assay PubMed 11795785PubMed 9395452. Source: MTBBASE

positive regulation of DNA repair

Inferred from genetic interaction Ref.9. Source: UniProtKB

response to antibiotic

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcell wall

Inferred from direct assay PubMed 20825248. Source: MTBBASE

cytosol

Inferred from direct assay PubMed 11967065PubMed 15525680. Source: MTBBASE

extracellular region

Inferred from direct assay PubMed 17443846. Source: MTBBASE

plasma membrane

Inferred from direct assay PubMed 14532352PubMed 15525680. Source: MTBBASE

   Molecular_functionNADH binding

Inferred from direct assay PubMed 9006925. Source: MTBBASE

NADPH binding

Inferred from direct assay PubMed 9006925. Source: MTBBASE

catalase activity

Inferred from direct assay PubMed 11795785PubMed 9006925PubMed 9395452. Source: MTBBASE

heme binding

Inferred from direct assay Ref.17PubMed 9006925. Source: MTBBASE

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

oxidoreductase activity, acting on a heme group of donors, nitrogenous group as acceptor

Inferred from direct assay PubMed 10080924. Source: MTBBASE

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 740740Catalase-peroxidase HAMAP-Rule MF_01961
PRO_0000055574

Sites

Active site1081Proton acceptor
Active site3211Tryptophan radical intermediate
Metal binding2701Iron (heme axial ligand)
Site1041Transition state stabilizer

Amino acid modifications

Cross-link107 ↔ 229Tryptophyl-tyrosyl-methioninium (Trp-Tyr) (with M-255) HAMAP-Rule MF_01961
Cross-link229 ↔ 255Tryptophyl-tyrosyl-methioninium (Tyr-Met) (with W-107) HAMAP-Rule MF_01961

Natural variations

Natural variant3001W → G in strain: H0892/92; INH-resistant.
Natural variant3151S → T in strain: H0181/94, H0452/92, H0948/92 and H0169/93; INH-resistant. Ref.18
Natural variant4631R → L in strain: H0169/93; INH-resistant.
Natural variant5011P → A in strain: H0948/92; INH-resistant.
Natural variant5251Q → P in strain: H0251/90; INH-resistant.
Natural variant5871L → P in strain: 15726/89; INH-resistant.
Natural variant7001S → P in strain: H0004/93; INH-resistant.

Experimental info

Sequence conflict2341G → A in CAA48213. Ref.1
Sequence conflict500 – 51213QPQVG…NDPDG → CSHKSGGRSTTRR in AAA72374. Ref.9

Secondary structure

.................................................................................................................................. 740
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q08129 [UniParc].

Last modified May 30, 2000. Version 3.
Checksum: B43C033B533CDD89

FASTA74080,605
        10         20         30         40         50         60 
MPEQHPPITE TTTGAASNGC PVVGHMKYPV EGGGNQDWWP NRLNLKVLHQ NPAVADPMGA 

        70         80         90        100        110        120 
AFDYAAEVAT IDVDALTRDI EEVMTTSQPW WPADYGHYGP LFIRMAWHAA GTYRIHDGRG 

       130        140        150        160        170        180 
GAGGGMQRFA PLNSWPDNAS LDKARRLLWP VKKKYGKKLS WADLIVFAGN CALESMGFKT 

       190        200        210        220        230        240 
FGFGFGRVDQ WEPDEVYWGK EATWLGDERY SGKRDLENPL AAVQMGLIYV NPEGPNGNPD 

       250        260        270        280        290        300 
PMAAAVDIRE TFRRMAMNDV ETAALIVGGH TFGKTHGAGP ADLVGPEPEA APLEQMGLGW 

       310        320        330        340        350        360 
KSSYGTGTGK DAITSGIEVV WTNTPTKWDN SFLEILYGYE WELTKSPAGA WQYTAKDGAG 

       370        380        390        400        410        420 
AGTIPDPFGG PGRSPTMLAT DLSLRVDPIY ERITRRWLEH PEELADEFAK AWYKLIHRDM 

       430        440        450        460        470        480 
GPVARYLGPL VPKQTLLWQD PVPAVSHDLV GEAEIASLKS QIRASGLTVS QLVSTAWAAA 

       490        500        510        520        530        540 
SSFRGSDKRG GANGGRIRLQ PQVGWEVNDP DGDLRKVIRT LEEIQESFNS AAPGNIKVSF 

       550        560        570        580        590        600 
ADLVVLGGCA AIEKAAKAAG HNITVPFTPG RTDASQEQTD VESFAVLEPK ADGFRNYLGK 

       610        620        630        640        650        660 
GNPLPAEYML LDKANLLTLS APEMTVLVGG LRVLGANYKR LPLGVFTEAS ESLTNDFFVN 

       670        680        690        700        710        720 
LLDMGITWEP SPADDGTYQG KDGSGKVKWT GSRVDLVFGS NSELRALVEV YGADDAQPKF 

       730        740 
VQDFVAAWDK VMNLDRFDVR 

« Hide

References

« Hide 'large scale' references
[1]"Characterization of the katG gene encoding a catalase-peroxidase required for the isoniazid susceptibility of Mycobacterium tuberculosis."
Heym B., Zhang Y., Poulet S., Young D., Cole S.T.
J. Bacteriol. 175:4255-4259(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], CHARACTERIZATION.
Strain: ATCC 25618 / H37Rv.
[2]Cole S.T.
Submitted (SEP-1994) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[3]"Rapid identification of a point mutation of the Mycobacterium tuberculosis catalase-peroxidase (katG) gene associated with isoniazid resistance."
Cockerill F.R. III, Uhl J.R., Temesgen Z., Zhang Y., Stockman L., Roberts G.D., Williams D.L., Kline B.C.
J. Infect. Dis. 171:240-245(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: ATCC 25618 / H37Rv.
[4]"katG gene mutations in isoniazid-resistant Mycobacterium tuberculosis strains isolated from Finnish patients."
Marttila H.J., Soini H., Huovinen P., Viljanen M.K.
Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: INH-resistant strains.
[5]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: ATCC 25618 / H37Rv.
[6]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: CDC 1551 / Oshkosh.
[7]"The catalase-peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis."
Zhang Y., Heym B., Allen B., Young D., Cole S.T.
Nature 358:591-593(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA], ISONIAZID RESISTANCE, DISRUPTION PHENOTYPE.
Strain: ATCC 25618 / H37Rv.
[8]Song J., Deretic V.
Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-94.
Strain: ATCC 25618 / H37Rv.
[9]"Involvement of the N- and C-terminal domains of Mycobacterium tuberculosis KatG in the protection of mutant Escherichia coli against DNA-damaging agents."
Mulder M.A., Nair S., Abratt V.R., Zappe H., Steyn L.M.
Microbiology 145:2011-2021(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 500-740, FUNCTION.
Strain: ATCC 25618 / H37Rv.
[10]"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] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[11]"Regulation of catalase-peroxidase (KatG) expression, isoniazid sensitivity and virulence by furA of Mycobacterium tuberculosis."
Pym A.S., Domenech P., Honore N., Song J., Deretic V., Cole S.T.
Mol. Microbiol. 40:879-889(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
Strain: ATCC 25618 / H37Rv.
[12]"The Met-Tyr-Trp cross-link in Mycobacterium tuberculosis catalase-peroxidase (KatG): autocatalytic formation and effect on enzyme catalysis and spectroscopic properties."
Ghiladi R.A., Knudsen G.M., Medzihradszky K.F., Ortiz de Montellano P.R.
J. Biol. Chem. 280:22651-22663(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: COVALENT BOND.
[13]"Redox intermediates in the catalase cycle of catalase-peroxidases from Synechocystis PCC 6803, Burkholderia pseudomallei, and Mycobacterium tuberculosis."
Jakopitsch C., Vlasits J., Wiseman B., Loewen P.C., Obinger C.
Biochemistry 46:1183-1193(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC MECHANISM.
[14]"Two [Fe(IV)=O Trp*] intermediates in M.tuberculosis catalase-peroxidase discriminated by multifrequency (9-285 GHz) EPR spectroscopy: reactivity toward isoniazid."
Singh R., Switala J., Loewen P.C., Ivancich A.
J. Am. Chem. Soc. 129:15954-15963(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: RADICAL INTERMEDIATE.
[15]"Comparative study of catalase-peroxidases (KatGs)."
Singh R., Wiseman B., Deemagarn T., Jha V., Switala J., Loewen P.C.
Arch. Biochem. Biophys. 471:207-214(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
[16]"targetTB: a target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis."
Raman K., Yeturu K., Chandra N.
BMC Syst. Biol. 2:109-109(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
[17]"Crystal structure of Mycobacterium tuberculosis catalase-peroxidase."
Bertrand T., Eady N.A.J., Jones J.N., Jesmin X., Nagy J.M., Jamart-Gregoire B., Raven E.L., Brown K.A.
J. Biol. Chem. 279:38991-38999(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.41 ANGSTROMS) OF 2-740.
[18]"Hydrogen peroxide-mediated isoniazid activation catalyzed by Mycobacterium tuberculosis catalase-peroxidase (KatG) and its S315T mutant."
Zhao X., Yu H., Yu S., Wang F., Sacchettini J.C., Magliozzo R.S.
Biochemistry 45:4131-4140(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF WILD-TYPE AND OF VARIANT THR-315 IN COMPLEX WITH HEME.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X68081 Genomic DNA. Translation: CAA48213.1.
U06258 Unassigned DNA. Translation: AAB04159.1.
U40593 Genomic DNA. Translation: AAA85167.1.
U40595 Genomic DNA. Translation: AAA85169.1.
U41305 Genomic DNA. Translation: AAA85171.1.
U41306 Genomic DNA. Translation: AAA85172.1.
U41307 Genomic DNA. Translation: AAA85173.1.
U41308 Genomic DNA. Translation: AAA85174.1.
U41309 Genomic DNA. Translation: AAA85175.1.
U41310 Genomic DNA. Translation: AAA85176.1.
U41311 Genomic DNA. Translation: AAA85177.1.
U41312 Genomic DNA. Translation: AAA85178.1.
U41313 Genomic DNA. Translation: AAA85179.1.
U41314 Genomic DNA. Translation: AAA85180.1.
BX842578 Genomic DNA. Translation: CAB10056.1.
AE000516 Genomic DNA. Translation: AAK46231.1.
AF002194 Genomic DNA. Translation: AAB63371.1.
L14268 Genomic DNA. Translation: AAA72374.1.
PIRA40662. A70519.
RefSeqNP_216424.1. NC_000962.3.
NP_336417.1. NC_002755.2.
YP_006515311.1. NC_018143.1.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1SFZmodel-A1-740[»]
1SJ2X-ray2.41A/B2-740[»]
2CCAX-ray2.00A/B1-740[»]
2CCDX-ray2.10A/B1-740[»]
ProteinModelPortalQ08129.
SMRQ08129. Positions 26-740.
ModBaseSearch...

Protein family/group databases

PeroxiBase3551. MtuCP01_H37rv.

Proteomic databases

PRIDEQ08129.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaAAK46231; AAK46231; MT1959.
GeneID13316702.
885638.
923602.
KEGGmtc:MT1959.
mtu:Rv1908c.
mtv:RVBD_1908c.
PATRIC18126074. VBIMycTub22151_2149.

Organism-specific databases

TubercuListRv1908c.

Phylogenomic databases

KOK03782.
OMAGPEVIWT.
ProtClustDBPRK15061.

Enzyme and pathway databases

ReactomeREACT_116125. Disease.

Family and domain databases

HAMAPMF_01961. Catal-peroxid.
InterProIPR000763. Catalase_peroxidase.
IPR010255. Haem_peroxidase.
IPR002016. Haem_peroxidase_pln/fun/bac.
IPR019794. Peroxidases_AS.
IPR019793. Peroxidases_heam-ligand_BS.
[Graphical view]
PfamPF00141. peroxidase. 2 hits.
[Graphical view]
PRINTSPR00460. BPEROXIDASE.
PR00458. PEROXIDASE.
SUPFAMSSF48113. Peroxidase_super. 2 hits.
TIGRFAMsTIGR00198. cat_per_HPI. 1 hit.
PROSITEPS00435. PEROXIDASE_1. 1 hit.
PS00436. PEROXIDASE_2. 1 hit.
PS50873. PEROXIDASE_4. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

DrugBankDB00609. Ethionamide.
DB00951. Isoniazid.
EvolutionaryTraceQ08129.

Entry information

Entry nameKATG_MYCTU
AccessionPrimary (citable) accession number: Q08129
Secondary accession number(s): O08221 expand/collapse secondary AC list , Q50544, Q50546, Q50551, Q50552, Q50553, Q50554, Q50555, Q50762, Q57215, Q57274
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: May 30, 2000
Last modified: May 1, 2013
This is version 112 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh

Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh: entries and gene names

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families