UniProtKB - P9WIE5 (KATG_MYCTU)
Protein
Catalase-peroxidase
Gene
katG
Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Status
Functioni
Bifunctional enzyme with both catalase and broad-spectrum peroxidase activity, oxidizing various electron donors including NADP(H) (PubMed:9006925, PubMed:18178143). Protects M.tuberculosis against toxic reactive oxygen species (ROS) including hydrogen peroxide as well as organic peroxides and thus contributes to its survival within host macrophages by countering the phagocyte oxidative burst (PubMed:8658136, PubMed:15165233). Also displays efficient peroxynitritase activity, which may help the bacterium to persist in macrophages (PubMed:10080924).UniRule annotation5 Publications
Might 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.1 Publication
Catalyzes the oxidative activation of the antitubercular pro-drug isoniazid (INH) to generate an isonicotinoyl radical that then reacts nonenzymatically with NAD to form an isonicotinoyl-NAD adduct which inhibits InhA.5 Publications
Miscellaneous
In contrast to the Synechocystis sp. enzyme, no Trp radical is formed on the distal Trp residue (Trp-91).1 Publication
Was identified as a high-confidence drug target.1 Publication
Many isoniazid-resistant clinical isolates contain mutations in katG, leading to abolition or reduction of catalase/peroxidase activity which results in lack of INH activation, or to a reduced affinity for INH. Other mechanisms of INH resistance include deletion of the katG gene, and down-regulation of katG expression due to mutations in the furA-katG intergenic region.Curated
Catalytic activityi
Cofactori
heme b2 PublicationsNote: Binds 1 heme b (iron(II)-protoporphyrin IX) group per subunit.2 Publications
Kineticsi
kcat is 10100 sec(-1) for the catalase reaction (at pH 7.0 and 25 degrees Celsius).1 Publication
- KM=2.4 mM for H2O2 in the catalase reaction (at pH 7.0)1 Publication
- KM=225 mM for H2O2 in the catalase reaction (at pH 5.5-6.0)1 Publication
- KM=5.18 mM for H2O2 in the catalase reaction (at pH 7.0 and 25 degrees Celsius)1 Publication
- KM=360 µM for H2O2 in the peroxidase reaction1 Publication
- KM=67 µM for ABTS1 Publication
- KM=192 µM for isoniazid (at pH 7.2)1 Publication
- Vmax=7620 µmol/min/mg enzyme for the catalase reaction (at pH 5.5-6.0)1 Publication
- Vmax=5700 µmol/min/mg enzyme for the catalase reaction (at pH 7.0)1 Publication
- Vmax=14 µmol/min/mg enzyme for the peroxidase reaction with ABTS as substrate1 Publication
pH dependencei
Optimum pH is 7.0 for the catalase activity and 4.5-5.5 for the peroxidase activity (PubMed:9006925). Optimum pH is 4.75 for the peroxidase activity (PubMed:18178143).2 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 104 | Transition state stabilizerUniRule annotation | 1 | |
Active sitei | 108 | Proton acceptorUniRule annotation | 1 | |
Metal bindingi | 270 | Iron (heme axial ligand); via tele nitrogenCombined sources3 Publications | 1 | |
Active sitei | 321 | Tryptophan radical intermediate1 Publication | 1 |
GO - Molecular functioni
- catalase activity Source: MTBBASE
- heme binding Source: MTBBASE
- metal ion binding Source: UniProtKB-KW
- NADH binding Source: MTBBASE
- NADPH binding Source: MTBBASE
- oxidoreductase activity, acting on a heme group of donors, nitrogenous group as acceptor Source: MTBBASE
- peroxidase activity Source: MTBBASE
GO - Biological processi
- cellular response to hydrogen peroxide Source: GO_Central
- evasion or tolerance by symbiont of host-produced reactive oxygen species Source: Reactome
- hydrogen peroxide catabolic process Source: MTBBASE
- pathogenesis Source: UniProtKB-KW
- positive regulation of DNA repair Source: UniProtKB
- response to oxidative stress Source: MTBBASE
Keywordsi
Molecular function | Oxidoreductase, Peroxidase |
Biological process | Antibiotic resistance, Hydrogen peroxide, Virulence |
Ligand | Heme, Iron, Metal-binding |
Enzyme and pathway databases
BioCyci | MetaCyc:G185E-6105-MONOMER MTBH37RV:G185E-6105-MONOMER |
Reactomei | R-HSA-1222387 Tolerance of reactive oxygen produced by macrophages |
Names & Taxonomyi
Protein namesi | Recommended name: Catalase-peroxidase2 PublicationsUniRule annotation (EC:1.11.1.21UniRule annotation2 Publications)Short name: CP1 PublicationUniRule annotation Alternative name(s): Peroxidase/catalaseUniRule annotation |
Gene namesi | Name:katG1 Publication Ordered Locus Names:Rv1908c ORF Names:MTCY180.10 |
Organismi | Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) |
Taxonomic identifieri | 83332 [NCBI] |
Taxonomic lineagei | Bacteria › Actinobacteria › Corynebacteriales › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex › |
Proteomesi |
|
Organism-specific databases
TubercuListi | Rv1908c |
Subcellular locationi
GO - Cellular componenti
- cell wall Source: MTBBASE
- cytosol Source: MTBBASE
- extracellular region Source: MTBBASE
- plasma membrane Source: MTBBASE
Pathology & Biotechi
Disruption phenotypei
Cells lacking this gene are devoid of catalase activity, supersensitive to H2O2 exposure and highly resistant to the antitubercular drug isoniazid (INH) in vitro. This mutant strain is markedly attenuated for virulence in mice and displays impaired growth in infected macrophages, but its growth and survival is indistinguishable from wild-type in macrophages lacking the ROS-generating NADPH oxidase (Phox).1 Publication
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 137 | D → S: Exhibits 8-fold increased catalytic efficiency for the activation of INH (INH-NAD formation). Possesses an enlarged substrate access channel. 1 Publication | 1 | |
Mutagenesisi | 229 | Y → F: Exhibits 2-fold increased affinity for INH. 1 Publication | 1 | |
Mutagenesisi | 315 | S → T: 20-fold decrease in the rate of INH-NAD adduct formation. Exhibits significantly reduced affinity for INH (KM is increased by 43-fold). 2 Publications | 1 | |
Mutagenesisi | 321 | W → F: Nearly no effect on the kinetic parameters for the activation of INH. 1 Publication | 1 | |
Mutagenesisi | 418 | R → L: Exhibits 1.7-fold decreased catalytic efficiency for the activation of INH. 1 Publication | 1 | |
Mutagenesisi | 463 | R → L: Nearly no effect on the kinetic parameters for the catalase and peroxidase activity. Activates INH and mediates InhA inactivation as efficiently as wild-type. 1 Publication | 1 |
Chemistry databases
DrugBanki | DB00609 Ethionamide DB00951 Isoniazid |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000055574 | 1 – 740 | Catalase-peroxidaseAdd BLAST | 740 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Cross-linki | 107 ↔ 229 | Tryptophyl-tyrosyl-methioninium (Trp-Tyr) (with M-255); alternateUniRule annotation1 Publication | ||
Cross-linki | 229 ↔ 255 | Tryptophyl-tyrosyl-methioninium (Tyr-Met) (with W-107); alternateUniRule annotation1 Publication |
Post-translational modificationi
Formation of the three residue Trp-Tyr-Met cross-link is important for the catalase, but not the peroxidase activity of the enzyme (By similarity). The formation of the Trp-Tyr-Met cross-link is autocatalytic (PubMed:15840564).UniRule annotation1 Publication
Keywords - PTMi
Organic radicalProteomic databases
PaxDbi | P9WIE5 |
Expressioni
Inductioni
Interactioni
Subunit structurei
Homodimer.
3 PublicationsProtein-protein interaction databases
STRINGi | 83332.Rv1908c |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P9WIE5 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domaini
Consists of two related domains. The catalase-peroxidase activity is associated with the N-terminal domain but no definite function has been assigned to the C-terminal domain, although it may play a role in substrate binding.1 Publication
Sequence similaritiesi
Phylogenomic databases
eggNOGi | ENOG4105C1X Bacteria COG0376 LUCA |
KOi | K03782 |
OMAi | GPETTWL |
PhylomeDBi | P9WIE5 |
Family and domain databases
HAMAPi | MF_01961 Catal_peroxid, 1 hit |
InterProi | View protein in InterPro IPR000763 Catalase_peroxidase IPR002016 Haem_peroxidase IPR010255 Haem_peroxidase_sf IPR019794 Peroxidases_AS IPR019793 Peroxidases_heam-ligand_BS |
PANTHERi | PTHR30555 PTHR30555, 1 hit |
Pfami | View protein in Pfam PF00141 peroxidase, 2 hits |
PRINTSi | PR00460 BPEROXIDASE PR00458 PEROXIDASE |
SUPFAMi | SSF48113 SSF48113, 2 hits |
TIGRFAMsi | TIGR00198 cat_per_HPI, 1 hit |
PROSITEi | View protein in PROSITE PS00435 PEROXIDASE_1, 1 hit PS00436 PEROXIDASE_2, 1 hit PS50873 PEROXIDASE_4, 1 hit |
i Sequence
Sequence statusi: Complete.
P9WIE5-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MPEQHPPITE TTTGAASNGC PVVGHMKYPV EGGGNQDWWP NRLNLKVLHQ
60 70 80 90 100
NPAVADPMGA AFDYAAEVAT IDVDALTRDI EEVMTTSQPW WPADYGHYGP
110 120 130 140 150
LFIRMAWHAA GTYRIHDGRG GAGGGMQRFA PLNSWPDNAS LDKARRLLWP
160 170 180 190 200
VKKKYGKKLS WADLIVFAGN CALESMGFKT FGFGFGRVDQ WEPDEVYWGK
210 220 230 240 250
EATWLGDERY SGKRDLENPL AAVQMGLIYV NPEGPNGNPD PMAAAVDIRE
260 270 280 290 300
TFRRMAMNDV ETAALIVGGH TFGKTHGAGP ADLVGPEPEA APLEQMGLGW
310 320 330 340 350
KSSYGTGTGK DAITSGIEVV WTNTPTKWDN SFLEILYGYE WELTKSPAGA
360 370 380 390 400
WQYTAKDGAG AGTIPDPFGG PGRSPTMLAT DLSLRVDPIY ERITRRWLEH
410 420 430 440 450
PEELADEFAK AWYKLIHRDM GPVARYLGPL VPKQTLLWQD PVPAVSHDLV
460 470 480 490 500
GEAEIASLKS QIRASGLTVS QLVSTAWAAA SSFRGSDKRG GANGGRIRLQ
510 520 530 540 550
PQVGWEVNDP DGDLRKVIRT LEEIQESFNS AAPGNIKVSF ADLVVLGGCA
560 570 580 590 600
AIEKAAKAAG HNITVPFTPG RTDASQEQTD VESFAVLEPK ADGFRNYLGK
610 620 630 640 650
GNPLPAEYML LDKANLLTLS APEMTVLVGG LRVLGANYKR LPLGVFTEAS
660 670 680 690 700
ESLTNDFFVN LLDMGITWEP SPADDGTYQG KDGSGKVKWT GSRVDLVFGS
710 720 730 740
NSELRALVEV YGADDAQPKF VQDFVAAWDK VMNLDRFDVR
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 234 | G → A in CAA48213 (PubMed:8320241).Curated | 1 | |
Sequence conflicti | 500 – 512 | QPQVG…NDPDG → CSHKSGGRSTTRR in AAA72374 (PubMed:10463167).CuratedAdd BLAST | 13 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural varianti | 300 | W → G in strain: H0892/92; INH-resistant. | 1 | |
Natural varianti | 315 | S → T in strain: H0181/94, H0452/92, H0948/92 and H0169/93; INH-resistant. | 1 | |
Natural varianti | 463 | R → L in strain: H0169/93; INH-resistant. | 1 | |
Natural varianti | 501 | P → A in strain: H0948/92; INH-resistant. | 1 | |
Natural varianti | 525 | Q → P in strain: H0251/90; INH-resistant. | 1 | |
Natural varianti | 587 | L → P in strain: 15726/89; INH-resistant. | 1 | |
Natural varianti | 700 | S → P in strain: H0004/93; INH-resistant. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 JX303265 Genomic DNA Translation: AFR90354.1 JX303270 Genomic DNA Translation: AFR90359.1 JX303273 Genomic DNA Translation: AFR90362.1 JX303276 Genomic DNA Translation: AFR90365.1 JX303277 Genomic DNA Translation: AFR90366.1 JX303278 Genomic DNA Translation: AFR90367.1 JX303280 Genomic DNA Translation: AFR90369.1 AL123456 Genomic DNA Translation: CCP44675.1 AF002194 Genomic DNA Translation: AAB63371.1 L14268 Genomic DNA Translation: AAA72374.1 |
PIRi | A70519 A40662 |
RefSeqi | NP_216424.1, NC_000962.3 WP_003899075.1, NZ_NVQJ01000034.1 |
Genome annotation databases
EnsemblBacteriai | CCP44675; CCP44675; Rv1908c |
GeneIDi | 885638 |
KEGGi | mtu:Rv1908c |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | 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 JX303265 Genomic DNA Translation: AFR90354.1 JX303270 Genomic DNA Translation: AFR90359.1 JX303273 Genomic DNA Translation: AFR90362.1 JX303276 Genomic DNA Translation: AFR90365.1 JX303277 Genomic DNA Translation: AFR90366.1 JX303278 Genomic DNA Translation: AFR90367.1 JX303280 Genomic DNA Translation: AFR90369.1 AL123456 Genomic DNA Translation: CCP44675.1 AF002194 Genomic DNA Translation: AAB63371.1 L14268 Genomic DNA Translation: AAA72374.1 |
PIRi | A70519 A40662 |
RefSeqi | NP_216424.1, NC_000962.3 WP_003899075.1, NZ_NVQJ01000034.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1SFZ | model | - | A | 1-740 | [»] | |
1SJ2 | X-ray | 2.41 | A/B | 2-740 | [»] | |
2CCA | X-ray | 2.00 | A/B | 1-740 | [»] | |
2CCD | X-ray | 2.10 | A/B | 1-740 | [»] | |
4C50 | X-ray | 2.50 | A/B | 1-740 | [»] | |
4C51 | X-ray | 3.10 | A/B | 1-740 | [»] | |
SMRi | P9WIE5 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
STRINGi | 83332.Rv1908c |
Chemistry databases
DrugBanki | DB00609 Ethionamide DB00951 Isoniazid |
Proteomic databases
PaxDbi | P9WIE5 |
Genome annotation databases
EnsemblBacteriai | CCP44675; CCP44675; Rv1908c |
GeneIDi | 885638 |
KEGGi | mtu:Rv1908c |
Organism-specific databases
TubercuListi | Rv1908c |
Phylogenomic databases
eggNOGi | ENOG4105C1X Bacteria COG0376 LUCA |
KOi | K03782 |
OMAi | GPETTWL |
PhylomeDBi | P9WIE5 |
Enzyme and pathway databases
BioCyci | MetaCyc:G185E-6105-MONOMER MTBH37RV:G185E-6105-MONOMER |
Reactomei | R-HSA-1222387 Tolerance of reactive oxygen produced by macrophages |
Family and domain databases
HAMAPi | MF_01961 Catal_peroxid, 1 hit |
InterProi | View protein in InterPro IPR000763 Catalase_peroxidase IPR002016 Haem_peroxidase IPR010255 Haem_peroxidase_sf IPR019794 Peroxidases_AS IPR019793 Peroxidases_heam-ligand_BS |
PANTHERi | PTHR30555 PTHR30555, 1 hit |
Pfami | View protein in Pfam PF00141 peroxidase, 2 hits |
PRINTSi | PR00460 BPEROXIDASE PR00458 PEROXIDASE |
SUPFAMi | SSF48113 SSF48113, 2 hits |
TIGRFAMsi | TIGR00198 cat_per_HPI, 1 hit |
PROSITEi | View protein in PROSITE PS00435 PEROXIDASE_1, 1 hit PS00436 PEROXIDASE_2, 1 hit PS50873 PEROXIDASE_4, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | KATG_MYCTU | |
Accessioni | P9WIE5Primary (citable) accession number: P9WIE5 Secondary accession number(s): J9VFD2 Q57274 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 16, 2014 |
Last sequence update: | April 16, 2014 | |
Last modified: | October 16, 2019 | |
This is version 46 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Prokaryotic Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Complete proteome, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families - 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