KATG_MYCTU
ID KATG_MYCTU Reviewed; 740 AA.
AC P9WIE5; J9VFD2; O08221; Q08129; Q50544; Q50546; Q50551; Q50552; Q50553;
AC Q50554; Q50555; Q50762; Q57215; Q57274;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 58.
DE RecName: Full=Catalase-peroxidase {ECO:0000255|HAMAP-Rule:MF_01961, ECO:0000303|PubMed:8320241, ECO:0000303|PubMed:9006925};
DE Short=CP {ECO:0000255|HAMAP-Rule:MF_01961, ECO:0000303|PubMed:15231843};
DE EC=1.11.1.21 {ECO:0000255|HAMAP-Rule:MF_01961, ECO:0000269|PubMed:18178143, ECO:0000269|PubMed:9006925};
DE AltName: Full=Peroxidase/catalase {ECO:0000255|HAMAP-Rule:MF_01961};
GN Name=katG {ECO:0000303|PubMed:8320241}; OrderedLocusNames=Rv1908c;
GN ORFNames=MTCY180.10;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=8320241; DOI=10.1128/jb.175.13.4255-4259.1993;
RA Heym B., Zhang Y., Poulet S., Young D., Cole S.T.;
RT "Characterization of the katG gene encoding a catalase-peroxidase required
RT for the isoniazid susceptibility of Mycobacterium tuberculosis.";
RL J. Bacteriol. 175:4255-4259(1993).
RN [2]
RP SEQUENCE REVISION.
RA Cole S.T.;
RL Submitted (SEP-1994) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=7798673; DOI=10.1093/infdis/171.1.240;
RA Cockerill F.R. III, Uhl J.R., Temesgen Z., Zhang Y., Stockman L.,
RA Roberts G.D., Williams D.L., Kline B.C.;
RT "Rapid identification of a point mutation of the Mycobacterium tuberculosis
RT catalase-peroxidase (katG) gene associated with isoniazid resistance.";
RL J. Infect. Dis. 171:240-245(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=INH-resistant strains;
RA Marttila H.J., Soini H., Huovinen P., Viljanen M.K.;
RT "katG gene mutations in isoniazid-resistant Mycobacterium tuberculosis
RT strains isolated from Finnish patients.";
RL Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=2937643, 3150565, 3264812, MTB001, MTB003, MTB005, and MTB007;
RX PubMed=22972833; DOI=10.1128/jcm.01893-12;
RA Daum L.T., Rodriguez J.D., Worthy S.A., Ismail N.A., Omar S.V.,
RA Dreyer A.W., Fourie P.B., Hoosen A.A., Chambers J.P., Fischer G.W.;
RT "Next-generation ion torrent sequencing of drug resistance mutations in
RT Mycobacterium tuberculosis strains.";
RL J. Clin. Microbiol. 50:3831-3837(2012).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [7]
RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION IN ISONIAZID
RP ACTIVATION, AND ISONIAZID RESISTANCE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=1501713; DOI=10.1038/358591a0;
RA Zhang Y., Heym B., Allen B., Young D., Cole S.T.;
RT "The catalase-peroxidase gene and isoniazid resistance of Mycobacterium
RT tuberculosis.";
RL Nature 358:591-593(1992).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-94.
RC STRAIN=ATCC 25618 / H37Rv;
RA Song J., Deretic V.;
RL Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 500-740, FUNCTION, AND DOMAIN.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=10463167; DOI=10.1099/13500872-145-8-2011;
RA Mulder M.A., Nair S., Abratt V.R., Zappe H., Steyn L.M.;
RT "Involvement of the N- and C-terminal domains of Mycobacterium tuberculosis
RT KatG in the protection of mutant Escherichia coli against DNA-damaging
RT agents.";
RL Microbiology 145:2011-2021(1999).
RN [10]
RP FUNCTION, AND INDUCTION.
RX PubMed=8658136; DOI=10.1126/science.272.5268.1641;
RA Sherman D.R., Mdluli K., Hickey M.J., Arain T.M., Morris S.L.,
RA Barry C.E. III, Stover C.K.;
RT "Compensatory ahpC gene expression in isoniazid-resistant Mycobacterium
RT tuberculosis.";
RL Science 272:1641-1643(1996).
RN [11]
RP FUNCTION AS A CATALASE-PEROXIDASE, CATALYTIC ACTIVITY, COFACTOR,
RP BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ARG-463, AND SUBUNIT.
RX PubMed=9006925; DOI=10.1074/jbc.272.5.2834;
RA Johnsson K., Froland W.A., Schultz P.G.;
RT "Overexpression, purification, and characterization of the catalase-
RT peroxidase KatG from Mycobacterium tuberculosis.";
RL J. Biol. Chem. 272:2834-2840(1997).
RN [12]
RP FUNCTION AS A PEROXYNITRITASE.
RX PubMed=10080924; DOI=10.1006/bbrc.1999.0358;
RA Wengenack N.L., Jensen M.P., Rusnak F., Stern M.K.;
RT "Mycobacterium tuberculosis KatG is a peroxynitritase.";
RL Biochem. Biophys. Res. Commun. 256:485-487(1999).
RN [13]
RP INDUCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=11401695; DOI=10.1046/j.1365-2958.2001.02427.x;
RA Pym A.S., Domenech P., Honore N., Song J., Deretic V., Cole S.T.;
RT "Regulation of catalase-peroxidase (KatG) expression, isoniazid sensitivity
RT and virulence by furA of Mycobacterium tuberculosis.";
RL Mol. Microbiol. 40:879-889(2001).
RN [14]
RP FUNCTION IN PATHOGENESIS, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 35801 / TMC 107 / Erdman;
RX PubMed=15165233; DOI=10.1111/j.1365-2958.2004.04078.x;
RA Ng V.H., Cox J.S., Sousa A.O., MacMicking J.D., McKinney J.D.;
RT "Role of KatG catalase-peroxidase in mycobacterial pathogenesis: countering
RT the phagocyte oxidative burst.";
RL Mol. Microbiol. 52:1291-1302(2004).
RN [15]
RP MET-TYR-TRP CROSS-LINK.
RX PubMed=15840564; DOI=10.1074/jbc.m502486200;
RA Ghiladi R.A., Knudsen G.M., Medzihradszky K.F., Ortiz de Montellano P.R.;
RT "The Met-Tyr-Trp cross-link in Mycobacterium tuberculosis catalase-
RT peroxidase (KatG): autocatalytic formation and effect on enzyme catalysis
RT and spectroscopic properties.";
RL J. Biol. Chem. 280:22651-22663(2005).
RN [16]
RP CATALYTIC MECHANISM.
RX PubMed=17260948; DOI=10.1021/bi062266+;
RA Jakopitsch C., Vlasits J., Wiseman B., Loewen P.C., Obinger C.;
RT "Redox intermediates in the catalase cycle of catalase-peroxidases from
RT Synechocystis PCC 6803, Burkholderia pseudomallei, and Mycobacterium
RT tuberculosis.";
RL Biochemistry 46:1183-1193(2007).
RN [17]
RP RADICAL INTERMEDIATE, AND ACTIVE SITE.
RX PubMed=18052167; DOI=10.1021/ja075108u;
RA Singh R., Switala J., Loewen P.C., Ivancich A.;
RT "Two [Fe(IV)=O Trp*] intermediates in M.tuberculosis catalase-peroxidase
RT discriminated by multifrequency (9-285 GHz) EPR spectroscopy: reactivity
RT toward isoniazid.";
RL J. Am. Chem. Soc. 129:15954-15963(2007).
RN [18]
RP FUNCTION AS A CATALASE-PEROXIDASE, CATALYTIC ACTIVITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=18178143; DOI=10.1016/j.abb.2007.12.008;
RA Singh R., Wiseman B., Deemagarn T., Jha V., Switala J., Loewen P.C.;
RT "Comparative study of catalase-peroxidases (KatGs).";
RL Arch. Biochem. Biophys. 471:207-214(2008).
RN [19]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [21]
RP DRUG RESISTANCE.
RX PubMed=21244531; DOI=10.1111/j.1365-2958.2011.07547.x;
RA Ando H., Kitao T., Miyoshi-Akiyama T., Kato S., Mori T., Kirikae T.;
RT "Downregulation of katG expression is associated with isoniazid resistance
RT in Mycobacterium tuberculosis.";
RL Mol. Microbiol. 79:1615-1628(2011).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.41 ANGSTROMS) OF 2-740 IN COMPLEX WITH HEME,
RP COFACTOR, TRP-TYR-MET CROSS-LINK, AND SUBUNIT.
RX PubMed=15231843; DOI=10.1074/jbc.m402382200;
RA Bertrand T., Eady N.A.J., Jones J.N., Jesmin X., Nagy J.M.,
RA Jamart-Gregoire B., Raven E.L., Brown K.A.;
RT "Crystal structure of Mycobacterium tuberculosis catalase-peroxidase.";
RL J. Biol. Chem. 279:38991-38999(2004).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF WILD-TYPE AND MUTANT THR-315 IN
RP COMPLEX WITH HEME, SUBUNIT, INH ACTIVATION, AND MUTAGENESIS OF SER-315.
RX PubMed=16566587; DOI=10.1021/bi051967o;
RA Zhao X., Yu H., Yu S., Wang F., Sacchettini J.C., Magliozzo R.S.;
RT "Hydrogen peroxide-mediated isoniazid activation catalyzed by Mycobacterium
RT tuberculosis catalase-peroxidase (KatG) and its S315T mutant.";
RL Biochemistry 45:4131-4140(2006).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF MUTANTS SER-137 AND LEU-418 IN
RP COMPLEX WITH HEME, FUNCTION IN INH ACTIVATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, DRUG RESISTANCE, AND MUTAGENESIS OF ASP-137; TYR-229; SER-315;
RP TRP-321 AND ARG-418.
RX PubMed=24185282; DOI=10.1039/c3cc47022a;
RA Zhao X., Hersleth H.P., Zhu J., Andersson K.K., Magliozzo R.S.;
RT "Access channel residues Ser315 and Asp137 in Mycobacterium tuberculosis
RT catalase-peroxidase (KatG) control peroxidatic activation of the pro-drug
RT isoniazid.";
RL Chem. Commun. (Camb.) 49:11650-11652(2013).
CC -!- FUNCTION: Bifunctional enzyme with both catalase and broad-spectrum
CC peroxidase activity, oxidizing various electron donors including
CC NADP(H) (PubMed:9006925, PubMed:18178143). Protects M.tuberculosis
CC against toxic reactive oxygen species (ROS) including hydrogen peroxide
CC as well as organic peroxides and thus contributes to its survival
CC within host macrophages by countering the phagocyte oxidative burst
CC (PubMed:8658136, PubMed:15165233). Also displays efficient
CC peroxynitritase activity, which may help the bacterium to persist in
CC macrophages (PubMed:10080924). {ECO:0000255|HAMAP-Rule:MF_01961,
CC ECO:0000269|PubMed:10080924, ECO:0000269|PubMed:15165233,
CC ECO:0000269|PubMed:18178143, ECO:0000269|PubMed:8658136,
CC ECO:0000269|PubMed:9006925}.
CC -!- FUNCTION: Might be involved in DNA repair. Partly complements recA-
CC deficient E.coli cells exposed to UV radiation, mitomycin C or hydrogen
CC peroxide. Increases resistance to mitomycin C in E.coli cells deficient
CC for either uvrA, uvrB or uvrC. {ECO:0000269|PubMed:10463167}.
CC -!- FUNCTION: Catalyzes the oxidative activation of the antitubercular pro-
CC drug isoniazid (INH) to generate an isonicotinoyl radical that then
CC reacts nonenzymatically with NAD to form an isonicotinoyl-NAD adduct
CC which inhibits InhA. {ECO:0000269|PubMed:16566587,
CC ECO:0000269|PubMed:18178143, ECO:0000269|PubMed:24185282,
CC ECO:0000269|PubMed:9006925, ECO:0000269|PubMed:9634230}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=AH2 + H2O2 = A + 2 H2O; Xref=Rhea:RHEA:30275,
CC ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:17499; EC=1.11.1.21; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_01961, ECO:0000269|PubMed:18178143,
CC ECO:0000269|PubMed:9006925};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H2O2 = 2 H2O + O2; Xref=Rhea:RHEA:20309, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16240; EC=1.11.1.21;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01961,
CC ECO:0000269|PubMed:18178143, ECO:0000269|PubMed:9006925};
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC Evidence={ECO:0000269|PubMed:15231843, ECO:0000269|PubMed:9006925};
CC Note=Binds 1 heme b (iron(II)-protoporphyrin IX) group per subunit.
CC {ECO:0000269|PubMed:15231843, ECO:0000269|PubMed:9006925};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.4 mM for H(2)O(2) in the catalase reaction (at pH 7.0)
CC {ECO:0000269|PubMed:18178143};
CC KM=225 mM for H(2)O(2) in the catalase reaction (at pH 5.5-6.0)
CC {ECO:0000269|PubMed:18178143};
CC KM=5.18 mM for H(2)O(2) in the catalase reaction (at pH 7.0 and 25
CC degrees Celsius) {ECO:0000269|PubMed:9006925};
CC KM=360 uM for H(2)O(2) in the peroxidase reaction
CC {ECO:0000269|PubMed:18178143};
CC KM=67 uM for ABTS {ECO:0000269|PubMed:18178143};
CC KM=192 uM for isoniazid (at pH 7.2) {ECO:0000269|PubMed:24185282};
CC Vmax=7620 umol/min/mg enzyme for the catalase reaction (at pH 5.5-
CC 6.0) {ECO:0000269|PubMed:18178143};
CC Vmax=5700 umol/min/mg enzyme for the catalase reaction (at pH 7.0)
CC {ECO:0000269|PubMed:18178143};
CC Vmax=14 umol/min/mg enzyme for the peroxidase reaction with ABTS as
CC substrate {ECO:0000269|PubMed:18178143};
CC Note=kcat is 10100 sec(-1) for the catalase reaction (at pH 7.0 and
CC 25 degrees Celsius). {ECO:0000269|PubMed:9006925};
CC pH dependence:
CC Optimum pH is 7.0 for the catalase activity and 4.5-5.5 for the
CC peroxidase activity (PubMed:9006925). Optimum pH is 4.75 for the
CC peroxidase activity (PubMed:18178143). {ECO:0000269|PubMed:18178143,
CC ECO:0000269|PubMed:9006925};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:15231843,
CC ECO:0000269|PubMed:16566587, ECO:0000269|PubMed:9006925}.
CC -!- INDUCTION: By treatment with H(2)O(2) (PubMed:8658136). Repressed by
CC FurA (PubMed:11401695). {ECO:0000269|PubMed:11401695,
CC ECO:0000269|PubMed:8658136}.
CC -!- DOMAIN: Consists of two related domains. The catalase-peroxidase
CC activity is associated with the N-terminal domain but no definite
CC function has been assigned to the C-terminal domain, although it may
CC play a role in substrate binding. {ECO:0000305|PubMed:10463167}.
CC -!- PTM: Formation of the three residue Trp-Tyr-Met cross-link is important
CC for the catalase, but not the peroxidase activity of the enzyme (By
CC similarity). The formation of the Trp-Tyr-Met cross-link is
CC autocatalytic (PubMed:15840564). {ECO:0000255|HAMAP-Rule:MF_01961,
CC ECO:0000269|PubMed:15840564}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene are devoid of catalase
CC activity, supersensitive to H(2)O(2) exposure and highly resistant to
CC the antitubercular drug isoniazid (INH) in vitro. This mutant strain is
CC markedly attenuated for virulence in mice and displays impaired growth
CC in infected macrophages, but its growth and survival is
CC indistinguishable from wild-type in macrophages lacking the ROS-
CC generating NADPH oxidase (Phox). {ECO:0000269|PubMed:15165233}.
CC -!- MISCELLANEOUS: In contrast to the Synechocystis sp. enzyme, no Trp
CC radical is formed on the distal Trp residue (Trp-91).
CC {ECO:0000269|PubMed:18052167}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000305|PubMed:19099550}.
CC -!- MISCELLANEOUS: Many isoniazid-resistant clinical isolates contain
CC mutations in katG, leading to abolition or reduction of
CC catalase/peroxidase activity which results in lack of INH activation,
CC or to a reduced affinity for INH. Other mechanisms of INH resistance
CC include deletion of the katG gene, and down-regulation of katG
CC expression due to mutations in the furA-katG intergenic region.
CC {ECO:0000305, ECO:0000305|PubMed:1501713, ECO:0000305|PubMed:21244531,
CC ECO:0000305|PubMed:24185282}.
CC -!- SIMILARITY: Belongs to the peroxidase family. Peroxidase/catalase
CC subfamily. {ECO:0000255|HAMAP-Rule:MF_01961}.
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DR EMBL; X68081; CAA48213.1; -; Genomic_DNA.
DR EMBL; U06258; AAB04159.1; -; Unassigned_DNA.
DR EMBL; U40593; AAA85167.1; -; Genomic_DNA.
DR EMBL; U40595; AAA85169.1; -; Genomic_DNA.
DR EMBL; U41305; AAA85171.1; -; Genomic_DNA.
DR EMBL; U41306; AAA85172.1; -; Genomic_DNA.
DR EMBL; U41307; AAA85173.1; -; Genomic_DNA.
DR EMBL; U41308; AAA85174.1; -; Genomic_DNA.
DR EMBL; U41309; AAA85175.1; -; Genomic_DNA.
DR EMBL; U41310; AAA85176.1; -; Genomic_DNA.
DR EMBL; U41311; AAA85177.1; -; Genomic_DNA.
DR EMBL; U41312; AAA85178.1; -; Genomic_DNA.
DR EMBL; U41313; AAA85179.1; -; Genomic_DNA.
DR EMBL; U41314; AAA85180.1; -; Genomic_DNA.
DR EMBL; JX303265; AFR90354.1; -; Genomic_DNA.
DR EMBL; JX303270; AFR90359.1; -; Genomic_DNA.
DR EMBL; JX303273; AFR90362.1; -; Genomic_DNA.
DR EMBL; JX303276; AFR90365.1; -; Genomic_DNA.
DR EMBL; JX303277; AFR90366.1; -; Genomic_DNA.
DR EMBL; JX303278; AFR90367.1; -; Genomic_DNA.
DR EMBL; JX303280; AFR90369.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP44675.1; -; Genomic_DNA.
DR EMBL; AF002194; AAB63371.1; -; Genomic_DNA.
DR EMBL; L14268; AAA72374.1; -; Genomic_DNA.
DR PIR; A70519; A40662.
DR RefSeq; NP_216424.1; NC_000962.3.
DR RefSeq; WP_003899075.1; NZ_NVQJ01000034.1.
DR PDB; 1SJ2; X-ray; 2.41 A; A/B=2-740.
DR PDB; 2CCA; X-ray; 2.00 A; A/B=1-740.
DR PDB; 2CCD; X-ray; 2.10 A; A/B=1-740.
DR PDB; 4C50; X-ray; 2.50 A; A/B=1-740.
DR PDB; 4C51; X-ray; 3.10 A; A/B=1-740.
DR PDB; 7A2I; EM; 3.30 A; A/B=1-740.
DR PDB; 7A7A; EM; 3.08 A; A/B=1-740.
DR PDB; 7A7C; EM; 3.16 A; A/B=1-740.
DR PDB; 7A8Z; EM; 3.35 A; A/B=1-740.
DR PDB; 7AA3; EM; 3.56 A; A/B=1-740.
DR PDB; 7AG8; EM; 2.68 A; A/B=1-740.
DR PDBsum; 1SJ2; -.
DR PDBsum; 2CCA; -.
DR PDBsum; 2CCD; -.
DR PDBsum; 4C50; -.
DR PDBsum; 4C51; -.
DR PDBsum; 7A2I; -.
DR PDBsum; 7A7A; -.
DR PDBsum; 7A7C; -.
DR PDBsum; 7A8Z; -.
DR PDBsum; 7AA3; -.
DR PDBsum; 7AG8; -.
DR AlphaFoldDB; P9WIE5; -.
DR SMR; P9WIE5; -.
DR STRING; 83332.Rv1908c; -.
DR DrugBank; DB00609; Ethionamide.
DR DrugBank; DB00951; Isoniazid.
DR PaxDb; P9WIE5; -.
DR ABCD; P9WIE5; 1 sequenced antibody.
DR DNASU; 885638; -.
DR GeneID; 885638; -.
DR KEGG; mtu:Rv1908c; -.
DR TubercuList; Rv1908c; -.
DR eggNOG; COG0376; Bacteria.
DR OMA; MILAGNC; -.
DR PhylomeDB; P9WIE5; -.
DR BioCyc; MetaCyc:G185E-6105-MON; -.
DR BRENDA; 1.11.1.21; 3445.
DR Reactome; R-HSA-1222387; Tolerance of reactive oxygen produced by macrophages.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IDA:MTBBASE.
DR GO; GO:0005576; C:extracellular region; HDA:MTBBASE.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0004096; F:catalase activity; IDA:MTBBASE.
DR GO; GO:0020037; F:heme binding; IDA:MTBBASE.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070404; F:NADH binding; IDA:MTBBASE.
DR GO; GO:0070402; F:NADPH binding; IDA:MTBBASE.
DR GO; GO:0016677; F:oxidoreductase activity, acting on a heme group of donors, nitrogenous group as acceptor; IDA:MTBBASE.
DR GO; GO:0004601; F:peroxidase activity; IDA:MTBBASE.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IBA:GO_Central.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IDA:MTBBASE.
DR GO; GO:0045739; P:positive regulation of DNA repair; IGI:UniProtKB.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR GO; GO:0006979; P:response to oxidative stress; IMP:MTBBASE.
DR HAMAP; MF_01961; Catal_peroxid; 1.
DR InterPro; IPR000763; Catalase_peroxidase.
DR InterPro; IPR002016; Haem_peroxidase.
DR InterPro; IPR010255; Haem_peroxidase_sf.
DR InterPro; IPR019794; Peroxidases_AS.
DR InterPro; IPR019793; Peroxidases_heam-ligand_BS.
DR PANTHER; PTHR30555; PTHR30555; 1.
DR Pfam; PF00141; peroxidase; 2.
DR PRINTS; PR00460; BPEROXIDASE.
DR PRINTS; PR00458; PEROXIDASE.
DR SUPFAM; SSF48113; SSF48113; 2.
DR TIGRFAMs; TIGR00198; cat_per_HPI; 1.
DR PROSITE; PS00435; PEROXIDASE_1; 1.
DR PROSITE; PS00436; PEROXIDASE_2; 1.
DR PROSITE; PS50873; PEROXIDASE_4; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic resistance; Heme; Hydrogen peroxide; Iron;
KW Metal-binding; Organic radical; Oxidoreductase; Peroxidase;
KW Reference proteome; Virulence.
FT CHAIN 1..740
FT /note="Catalase-peroxidase"
FT /id="PRO_0000055574"
FT ACT_SITE 108
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01961"
FT ACT_SITE 321
FT /note="Tryptophan radical intermediate"
FT /evidence="ECO:0000269|PubMed:18052167"
FT BINDING 270
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000269|PubMed:15231843,
FT ECO:0000269|PubMed:16566587, ECO:0000269|PubMed:24185282,
FT ECO:0007744|PDB:1SJ2, ECO:0007744|PDB:2CCA,
FT ECO:0007744|PDB:2CCD, ECO:0007744|PDB:4C51"
FT SITE 104
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01961"
FT CROSSLNK 107..229
FT /note="Tryptophyl-tyrosyl-methioninium (Trp-Tyr) (with M-
FT 255); alternate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01961,
FT ECO:0000269|PubMed:15231843"
FT CROSSLNK 229..255
FT /note="Tryptophyl-tyrosyl-methioninium (Tyr-Met) (with W-
FT 107); alternate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01961,
FT ECO:0000269|PubMed:15231843"
FT VARIANT 300
FT /note="W -> G (in strain: H0892/92; INH-resistant)"
FT VARIANT 315
FT /note="S -> T (in strain: H0181/94, H0452/92, H0948/92 and
FT H0169/93; INH-resistant)"
FT VARIANT 463
FT /note="R -> L (in strain: H0169/93; INH-resistant)"
FT VARIANT 501
FT /note="P -> A (in strain: H0948/92; INH-resistant)"
FT VARIANT 525
FT /note="Q -> P (in strain: H0251/90; INH-resistant)"
FT VARIANT 587
FT /note="L -> P (in strain: 15726/89; INH-resistant)"
FT VARIANT 700
FT /note="S -> P (in strain: H0004/93; INH-resistant)"
FT MUTAGEN 137
FT /note="D->S: Exhibits 8-fold increased catalytic efficiency
FT for the activation of INH (INH-NAD formation). Possesses an
FT enlarged substrate access channel."
FT /evidence="ECO:0000269|PubMed:24185282"
FT MUTAGEN 229
FT /note="Y->F: Exhibits 2-fold increased affinity for INH."
FT /evidence="ECO:0000269|PubMed:24185282"
FT MUTAGEN 315
FT /note="S->T: 20-fold decrease in the rate of INH-NAD adduct
FT formation. Exhibits significantly reduced affinity for INH
FT (KM is increased by 43-fold)."
FT /evidence="ECO:0000269|PubMed:16566587,
FT ECO:0000269|PubMed:24185282"
FT MUTAGEN 321
FT /note="W->F: Nearly no effect on the kinetic parameters for
FT the activation of INH."
FT /evidence="ECO:0000269|PubMed:24185282"
FT MUTAGEN 418
FT /note="R->L: Exhibits 1.7-fold decreased catalytic
FT efficiency for the activation of INH."
FT /evidence="ECO:0000269|PubMed:24185282"
FT MUTAGEN 463
FT /note="R->L: Nearly no effect on the kinetic parameters for
FT the catalase and peroxidase activity. Activates INH and
FT mediates InhA inactivation as efficiently as wild-type."
FT /evidence="ECO:0000269|PubMed:9006925"
FT CONFLICT 234
FT /note="G -> A (in Ref. 1; CAA48213)"
FT /evidence="ECO:0000305"
FT CONFLICT 500..512
FT /note="QPQVGWEVNDPDG -> CSHKSGGRSTTRR (in Ref. 9;
FT AAA72374)"
FT /evidence="ECO:0000305"
FT HELIX 29..31
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 35..37
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 45..48
FT /evidence="ECO:0007829|PDB:2CCA"
FT STRAND 49..51
FT /evidence="ECO:0007829|PDB:7A2I"
FT HELIX 53..55
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 64..68
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 73..84
FT /evidence="ECO:0007829|PDB:2CCA"
FT STRAND 89..91
FT /evidence="ECO:0007829|PDB:7A8Z"
FT HELIX 94..96
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 99..110
FT /evidence="ECO:0007829|PDB:2CCA"
FT TURN 115..117
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 122..124
FT /evidence="ECO:0007829|PDB:2CCD"
FT HELIX 126..128
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 132..134
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 136..138
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 141..146
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 149..155
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 161..175
FT /evidence="ECO:0007829|PDB:2CCA"
FT TURN 212..214
FT /evidence="ECO:0007829|PDB:2CCA"
FT STRAND 222..224
FT /evidence="ECO:0007829|PDB:2CCA"
FT STRAND 228..230
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 235..237
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 241..253
FT /evidence="ECO:0007829|PDB:2CCA"
FT TURN 254..256
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 259..270
FT /evidence="ECO:0007829|PDB:2CCA"
FT STRAND 277..279
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 281..283
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 288..290
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 293..295
FT /evidence="ECO:0007829|PDB:2CCA"
FT STRAND 300..302
FT /evidence="ECO:0007829|PDB:7A7A"
FT HELIX 309..311
FT /evidence="ECO:0007829|PDB:2CCA"
FT STRAND 313..316
FT /evidence="ECO:0007829|PDB:2CCA"
FT STRAND 322..324
FT /evidence="ECO:0007829|PDB:7A2I"
FT HELIX 331..338
FT /evidence="ECO:0007829|PDB:2CCA"
FT STRAND 341..345
FT /evidence="ECO:0007829|PDB:2CCA"
FT STRAND 347..349
FT /evidence="ECO:0007829|PDB:7A7C"
FT STRAND 351..355
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 356..358
FT /evidence="ECO:0007829|PDB:2CCA"
FT TURN 359..362
FT /evidence="ECO:0007829|PDB:2CCA"
FT STRAND 367..369
FT /evidence="ECO:0007829|PDB:1SJ2"
FT HELIX 379..386
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 388..399
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 401..417
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 418..420
FT /evidence="ECO:0007829|PDB:1SJ2"
FT HELIX 423..425
FT /evidence="ECO:0007829|PDB:2CCA"
FT STRAND 427..429
FT /evidence="ECO:0007829|PDB:7A7A"
FT HELIX 437..439
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 452..463
FT /evidence="ECO:0007829|PDB:2CCA"
FT TURN 464..466
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 469..480
FT /evidence="ECO:0007829|PDB:2CCA"
FT TURN 485..488
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 496..498
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 502..504
FT /evidence="ECO:0007829|PDB:2CCA"
FT TURN 506..508
FT /evidence="ECO:0007829|PDB:4C50"
FT TURN 510..513
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 514..531
FT /evidence="ECO:0007829|PDB:2CCA"
FT STRAND 533..536
FT /evidence="ECO:0007829|PDB:1SJ2"
FT HELIX 540..558
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 576..578
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 581..584
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 585..587
FT /evidence="ECO:0007829|PDB:2CCA"
FT STRAND 590..592
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 593..595
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 606..616
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 621..633
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 638..640
FT /evidence="ECO:0007829|PDB:2CCA"
FT STRAND 642..644
FT /evidence="ECO:0007829|PDB:7A2I"
FT STRAND 648..651
FT /evidence="ECO:0007829|PDB:4C50"
FT HELIX 656..661
FT /evidence="ECO:0007829|PDB:2CCA"
FT STRAND 667..670
FT /evidence="ECO:0007829|PDB:2CCA"
FT STRAND 675..681
FT /evidence="ECO:0007829|PDB:2CCA"
FT STRAND 683..685
FT /evidence="ECO:0007829|PDB:2CCD"
FT STRAND 687..692
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 693..700
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 702..711
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 714..716
FT /evidence="ECO:0007829|PDB:4C51"
FT HELIX 717..732
FT /evidence="ECO:0007829|PDB:2CCA"
FT TURN 733..735
FT /evidence="ECO:0007829|PDB:2CCA"
FT HELIX 737..739
FT /evidence="ECO:0007829|PDB:2CCA"
SQ SEQUENCE 740 AA; 80605 MW; B43C033B533CDD89 CRC64;
MPEQHPPITE TTTGAASNGC PVVGHMKYPV EGGGNQDWWP NRLNLKVLHQ NPAVADPMGA
AFDYAAEVAT IDVDALTRDI EEVMTTSQPW WPADYGHYGP LFIRMAWHAA GTYRIHDGRG
GAGGGMQRFA PLNSWPDNAS LDKARRLLWP VKKKYGKKLS WADLIVFAGN CALESMGFKT
FGFGFGRVDQ WEPDEVYWGK EATWLGDERY SGKRDLENPL AAVQMGLIYV NPEGPNGNPD
PMAAAVDIRE TFRRMAMNDV ETAALIVGGH TFGKTHGAGP ADLVGPEPEA APLEQMGLGW
KSSYGTGTGK DAITSGIEVV WTNTPTKWDN SFLEILYGYE WELTKSPAGA WQYTAKDGAG
AGTIPDPFGG PGRSPTMLAT DLSLRVDPIY ERITRRWLEH PEELADEFAK AWYKLIHRDM
GPVARYLGPL VPKQTLLWQD PVPAVSHDLV GEAEIASLKS QIRASGLTVS QLVSTAWAAA
SSFRGSDKRG GANGGRIRLQ PQVGWEVNDP DGDLRKVIRT LEEIQESFNS AAPGNIKVSF
ADLVVLGGCA AIEKAAKAAG HNITVPFTPG RTDASQEQTD VESFAVLEPK ADGFRNYLGK
GNPLPAEYML LDKANLLTLS APEMTVLVGG LRVLGANYKR LPLGVFTEAS ESLTNDFFVN
LLDMGITWEP SPADDGTYQG KDGSGKVKWT GSRVDLVFGS NSELRALVEV YGADDAQPKF
VQDFVAAWDK VMNLDRFDVR
