KATG_MYCTO
ID KATG_MYCTO Reviewed; 740 AA.
AC P9WIE4; 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 39.
DE RecName: Full=Catalase-peroxidase {ECO:0000255|HAMAP-Rule:MF_01961};
DE Short=CP {ECO:0000255|HAMAP-Rule:MF_01961};
DE EC=1.11.1.21 {ECO:0000255|HAMAP-Rule:MF_01961};
DE AltName: Full=Peroxidase/catalase {ECO:0000255|HAMAP-Rule:MF_01961};
GN Name=katG {ECO:0000255|HAMAP-Rule:MF_01961}; OrderedLocusNames=MT1959;
OS Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83331;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CDC 1551 / Oshkosh;
RX PubMed=12218036; DOI=10.1128/jb.184.19.5479-5490.2002;
RA Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O.,
RA Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K.,
RA Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L.,
RA Delcher A., Utterback T.R., Weidman J.F., Khouri H.M., Gill J., Mikula A.,
RA Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M.;
RT "Whole-genome comparison of Mycobacterium tuberculosis clinical and
RT laboratory strains.";
RL J. Bacteriol. 184:5479-5490(2002).
CC -!- FUNCTION: Bifunctional enzyme with both catalase and broad-spectrum
CC peroxidase activity, oxidizing various electron donors including
CC NADP(H). Protects M.tuberculosis against toxic reactive oxygen species
CC (ROS) including hydrogen peroxide as well as organic peroxides and thus
CC contributes to its survival within host macrophages by countering the
CC phagocyte oxidative burst. Also displays efficient peroxynitritase
CC activity, which may help the bacterium to persist in macrophages.
CC {ECO:0000250|UniProtKB:P9WIE5, ECO:0000255|HAMAP-Rule:MF_01961}.
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:0000250|UniProtKB:P9WIE5}.
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};
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 -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01961};
CC Note=Binds 1 heme b (iron(II)-protoporphyrin IX) group per subunit.
CC {ECO:0000255|HAMAP-Rule:MF_01961};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P9WIE5}.
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.
CC {ECO:0000255|HAMAP-Rule:MF_01961}.
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:0000250|UniProtKB:P9WIE5, ECO:0000305}.
CC -!- SIMILARITY: Belongs to the peroxidase family. Peroxidase/catalase
CC subfamily. {ECO:0000255|HAMAP-Rule:MF_01961}.
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DR EMBL; AE000516; AAK46231.1; -; Genomic_DNA.
DR PIR; A70519; A40662.
DR RefSeq; WP_003899075.1; NZ_KK341227.1.
DR AlphaFoldDB; P9WIE4; -.
DR SMR; P9WIE4; -.
DR DrugCentral; P9WIE4; -.
DR EnsemblBacteria; AAK46231; AAK46231; MT1959.
DR KEGG; mtc:MT1959; -.
DR PATRIC; fig|83331.31.peg.2109; -.
DR HOGENOM; CLU_025424_2_0_11; -.
DR Proteomes; UP000001020; Chromosome.
DR GO; GO:0004096; F:catalase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR GO; GO:0006979; P:response to oxidative stress; IEA:InterPro.
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 3: Inferred from homology;
KW Antibiotic resistance; Heme; Hydrogen peroxide; Iron; Metal-binding;
KW Organic radical; Oxidoreductase; Peroxidase; Virulence.
FT CHAIN 1..740
FT /note="Catalase-peroxidase"
FT /id="PRO_0000428021"
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:0000250|UniProtKB:P9WIE5"
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:0000255|HAMAP-Rule:MF_01961"
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)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01961"
FT CROSSLNK 229..255
FT /note="Tryptophyl-tyrosyl-methioninium (Tyr-Met) (with W-
FT 107)"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01961"
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
