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Protein

Catalase-peroxidase

Gene

katG

Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

Catalytic activityi

Donor + H2O2 = oxidized donor + 2 H2O.UniRule annotation2 Publications
2 H2O2 = O2 + 2 H2O.UniRule annotation2 Publications

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

Manual assertion based on experiment ini

  1. KM=2.4 mM for H2O2 in the catalase reaction (at pH 7.0)1 Publication
  2. KM=225 mM for H2O2 in the catalase reaction (at pH 5.5-6.0)1 Publication
  3. KM=5.18 mM for H2O2 in the catalase reaction (at pH 7.0 and 25 degrees Celsius)1 Publication
  4. KM=360 µM for H2O2 in the peroxidase reaction1 Publication
  5. KM=67 µM for ABTS1 Publication
  6. KM=192 µM for isoniazid (at pH 7.2)1 Publication
  1. Vmax=7620 µmol/min/mg enzyme for the catalase reaction (at pH 5.5-6.0)1 Publication
  2. Vmax=5700 µmol/min/mg enzyme for the catalase reaction (at pH 7.0)1 Publication
  3. 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 keyPosition(s)DescriptionActionsGraphical viewLength
Sitei104Transition state stabilizerUniRule annotation1
Active sitei108Proton acceptorUniRule annotation1
Metal bindingi270Iron (heme axial ligand); via tele nitrogenCombined sources3 Publications1
Active sitei321Tryptophan radical intermediate1 Publication1

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

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase, Peroxidase

Keywords - Biological processi

Antibiotic resistance, Hydrogen peroxide, Virulence

Keywords - Ligandi

Heme, Iron, Metal-binding

Enzyme and pathway databases

BioCyciMTBH37RV:G185E-6105-MONOMER.
ReactomeiR-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
OrganismiMycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Taxonomic identifieri83332 [NCBI]
Taxonomic lineageiBacteriaActinobacteriaCorynebacterialesMycobacteriaceaeMycobacteriumMycobacterium tuberculosis complex
Proteomesi
  • UP000001584 Componenti: Chromosome

Organism-specific databases

TubercuListiRv1908c.

Subcellular locationi

GO - Cellular componenti

  • cell wall Source: MTBBASE
  • cytosol Source: MTBBASE
  • extracellular region Source: MTBBASE
  • plasma membrane Source: MTBBASE
Complete GO annotation...

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 keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi137D → S: Exhibits 8-fold increased catalytic efficiency for the activation of INH (INH-NAD formation). Possesses an enlarged substrate access channel. 1 Publication1
Mutagenesisi229Y → F: Exhibits 2-fold increased affinity for INH. 1 Publication1
Mutagenesisi315S → 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 Publications1
Mutagenesisi321W → F: Nearly no effect on the kinetic parameters for the activation of INH. 1 Publication1
Mutagenesisi418R → L: Exhibits 1.7-fold decreased catalytic efficiency for the activation of INH. 1 Publication1
Mutagenesisi463R → 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 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000555741 – 740Catalase-peroxidaseAdd BLAST740

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki107 ↔ 229Tryptophyl-tyrosyl-methioninium (Trp-Tyr) (with M-255); alternateUniRule annotation1 Publication
Cross-linki229 ↔ 255Tryptophyl-tyrosyl-methioninium (Tyr-Met) (with W-107); alternateUniRule annotation1 Publication

Post-translational modificationi

The covalent Trp-Tyr-Met adduct 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 radical

Proteomic databases

PaxDbiP9WIE5.

Expressioni

Inductioni

By treatment with H2O2 (PubMed:8658136). Repressed by FurA (PubMed:11401695).2 Publications

Interactioni

Subunit structurei

Homodimer.3 Publications

Protein-protein interaction databases

STRINGi83332.Rv1908c.

Structurei

Secondary structure

1740
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi29 – 31Combined sources3
Helixi35 – 37Combined sources3
Helixi45 – 48Combined sources4
Helixi53 – 55Combined sources3
Helixi64 – 68Combined sources5
Helixi73 – 84Combined sources12
Helixi94 – 96Combined sources3
Helixi99 – 110Combined sources12
Turni115 – 117Combined sources3
Helixi122 – 124Combined sources3
Helixi126 – 128Combined sources3
Helixi132 – 134Combined sources3
Helixi136 – 138Combined sources3
Helixi141 – 146Combined sources6
Helixi149 – 155Combined sources7
Helixi156 – 158Combined sources3
Helixi161 – 175Combined sources15
Turni212 – 214Combined sources3
Beta strandi222 – 224Combined sources3
Beta strandi228 – 230Combined sources3
Helixi235 – 237Combined sources3
Helixi241 – 253Combined sources13
Turni254 – 256Combined sources3
Helixi259 – 270Combined sources12
Beta strandi277 – 279Combined sources3
Helixi281 – 283Combined sources3
Helixi288 – 290Combined sources3
Helixi293 – 295Combined sources3
Helixi309 – 311Combined sources3
Beta strandi313 – 316Combined sources4
Helixi331 – 338Combined sources8
Beta strandi341 – 345Combined sources5
Beta strandi351 – 355Combined sources5
Helixi356 – 358Combined sources3
Turni359 – 362Combined sources4
Beta strandi367 – 369Combined sources3
Helixi379 – 386Combined sources8
Helixi388 – 399Combined sources12
Helixi401 – 417Combined sources17
Helixi418 – 420Combined sources3
Helixi423 – 425Combined sources3
Helixi437 – 439Combined sources3
Helixi452 – 463Combined sources12
Turni464 – 466Combined sources3
Helixi469 – 480Combined sources12
Turni485 – 488Combined sources4
Helixi496 – 498Combined sources3
Helixi502 – 504Combined sources3
Turni510 – 513Combined sources4
Helixi514 – 531Combined sources18
Beta strandi533 – 536Combined sources4
Helixi540 – 558Combined sources19
Helixi576 – 578Combined sources3
Helixi581 – 584Combined sources4
Helixi585 – 587Combined sources3
Beta strandi590 – 592Combined sources3
Helixi593 – 595Combined sources3
Helixi606 – 616Combined sources11
Helixi621 – 633Combined sources13
Helixi638 – 640Combined sources3
Helixi656 – 661Combined sources6
Beta strandi667 – 670Combined sources4
Beta strandi675 – 681Combined sources7
Beta strandi683 – 685Combined sources3
Beta strandi687 – 692Combined sources6
Helixi693 – 700Combined sources8
Helixi702 – 711Combined sources10
Helixi717 – 732Combined sources16
Turni733 – 735Combined sources3
Helixi737 – 739Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1SFZmodel-A1-740[»]
1SJ2X-ray2.41A/B2-740[»]
2CCAX-ray2.00A/B1-740[»]
2CCDX-ray2.10A/B1-740[»]
4C50X-ray2.50A/B1-740[»]
4C51X-ray3.10A/B1-740[»]
ProteinModelPortaliP9WIE5.
SMRiP9WIE5.
ModBaseiSearch...
MobiDBiSearch...

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

Belongs to the peroxidase family. Peroxidase/catalase subfamily.UniRule annotation

Phylogenomic databases

eggNOGiENOG4105C1X. Bacteria.
COG0376. LUCA.
KOiK03782.
OMAiIAEVYAC.
PhylomeDBiP9WIE5.

Family and domain databases

HAMAPiMF_01961. Catal_peroxid. 1 hit.
InterProiIPR000763. Catalase_peroxidase.
IPR010255. Haem_peroxidase.
IPR002016. Haem_peroxidase_pln/fun/bac.
IPR019794. Peroxidases_AS.
IPR019793. Peroxidases_heam-ligand_BS.
[Graphical view]
PfamiPF00141. peroxidase. 2 hits.
[Graphical view]
PRINTSiPR00460. BPEROXIDASE.
PR00458. PEROXIDASE.
SUPFAMiSSF48113. SSF48113. 2 hits.
TIGRFAMsiTIGR00198. cat_per_HPI. 1 hit.
PROSITEiPS00435. PEROXIDASE_1. 1 hit.
PS00436. PEROXIDASE_2. 1 hit.
PS50873. PEROXIDASE_4. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P9WIE5-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:740
Mass (Da):80,605
Last modified:April 16, 2014 - v1
Checksum:iB43C033B533CDD89
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti234G → A in CAA48213 (PubMed:8320241).Curated1
Sequence conflicti500 – 512QPQVG…NDPDG → CSHKSGGRSTTRR in AAA72374 (PubMed:10463167).CuratedAdd BLAST13

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti300W → G in strain: H0892/92; INH-resistant. 1
Natural varianti315S → T in strain: H0181/94, H0452/92, H0948/92 and H0169/93; INH-resistant. 1
Natural varianti463R → L in strain: H0169/93; INH-resistant. 1
Natural varianti501P → A in strain: H0948/92; INH-resistant. 1
Natural varianti525Q → P in strain: H0251/90; INH-resistant. 1
Natural varianti587L → P in strain: 15726/89; INH-resistant. 1
Natural varianti700S → 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.
PIRiA70519. A40662.
RefSeqiNP_216424.1. NC_000962.3.
WP_003899075.1. NZ_KK339370.1.

Genome annotation databases

EnsemblBacteriaiCCP44675; CCP44675; Rv1908c.
GeneIDi885638.
KEGGimtu:Rv1908c.

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.
PIRiA70519. A40662.
RefSeqiNP_216424.1. NC_000962.3.
WP_003899075.1. NZ_KK339370.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1SFZmodel-A1-740[»]
1SJ2X-ray2.41A/B2-740[»]
2CCAX-ray2.00A/B1-740[»]
2CCDX-ray2.10A/B1-740[»]
4C50X-ray2.50A/B1-740[»]
4C51X-ray3.10A/B1-740[»]
ProteinModelPortaliP9WIE5.
SMRiP9WIE5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi83332.Rv1908c.

Proteomic databases

PaxDbiP9WIE5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiCCP44675; CCP44675; Rv1908c.
GeneIDi885638.
KEGGimtu:Rv1908c.

Organism-specific databases

TubercuListiRv1908c.

Phylogenomic databases

eggNOGiENOG4105C1X. Bacteria.
COG0376. LUCA.
KOiK03782.
OMAiIAEVYAC.
PhylomeDBiP9WIE5.

Enzyme and pathway databases

BioCyciMTBH37RV:G185E-6105-MONOMER.
ReactomeiR-HSA-1222387. Tolerance of reactive oxygen produced by macrophages.

Family and domain databases

HAMAPiMF_01961. Catal_peroxid. 1 hit.
InterProiIPR000763. Catalase_peroxidase.
IPR010255. Haem_peroxidase.
IPR002016. Haem_peroxidase_pln/fun/bac.
IPR019794. Peroxidases_AS.
IPR019793. Peroxidases_heam-ligand_BS.
[Graphical view]
PfamiPF00141. peroxidase. 2 hits.
[Graphical view]
PRINTSiPR00460. BPEROXIDASE.
PR00458. PEROXIDASE.
SUPFAMiSSF48113. SSF48113. 2 hits.
TIGRFAMsiTIGR00198. cat_per_HPI. 1 hit.
PROSITEiPS00435. PEROXIDASE_1. 1 hit.
PS00436. PEROXIDASE_2. 1 hit.
PS50873. PEROXIDASE_4. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKATG_MYCTU
AccessioniPrimary (citable) accession number: P9WIE5
Secondary accession number(s): J9VFD2
, O08221, Q08129, Q50544, Q50546, Q50551, Q50552, Q50553, Q50554, Q50555, Q50762, Q57215, Q57274
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 16, 2014
Last sequence update: April 16, 2014
Last modified: November 30, 2016
This is version 25 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh
    Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh: entries and gene names
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.