Reviewed, UniProtKB/Swiss-Prot Q08129 (KATG_MYCTU)

Names and origin

Protein names

Recommended name:
    Catalase-peroxidase
      Short name=CP
    EC=1.11.1.6
    EC=1.11.1.7
Alternative name(s):
    Peroxidase/catalase

Gene names

Name:	katG
Ordered Locus Names:	Rv1908c, MT1959
ORF Names:	MTCY180.10

Organism

Mycobacterium tuberculosis [Complete proteome] [HAMAP]

Taxonomic identifier

1773 [NCBI]

Taxonomic lineage

Bacteria › Actinobacteria › Actinobacteridae › Actinomycetales › Corynebacterineae › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex

Protein attributes

Sequence length	740 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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. HAMAP MF_01961
Catalytic activity	2 H2O2 = O2 + 2 H2O. HAMAP MF_01961 Donor + H2O2 = oxidized donor + 2 H2O. HAMAP MF_01961
Cofactor	Binds 1 heme B (iron-protoporphyrin IX) group per subunit. HAMAP MF_01961
Subunit structure	Homodimer. HAMAP MF_01961
Post-translational modification	The covalent Trp-Tyr-Met adduct is important for the catalase, but not the peroxidase activity of the enzyme By similarity.
Disruption phenotype	Cells show isoniazid (INH) resistance. Ref.7
Miscellaneous	In contrast to the Synechocystis sp. enzyme, no Trp radical is formed on the distal Trp residue (Trp-91). HAMAP 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 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) HAMAP MF_01961 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 process	Hydrogen peroxide
Ligand	Heme Iron Metal-binding
Molecular function	Oxidoreductase Peroxidase
PTM	Organic radical
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	hydrogen peroxide catabolic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	catalase activity Inferred from electronic annotation. Source: HAMAP heme binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 740

740

Catalase-peroxidase HAMAP MF_01961

PRO_0000055574

Sites

Active site

108

1

Proton acceptor HAMAP MF_01961

Active site

321

1

Tryptophan radical intermediate HAMAP MF_01961

Metal binding

270

1

Iron (heme axial ligand) HAMAP MF_01961

Site

104

1

Transition state stabilizer HAMAP MF_01961

Amino acid modifications

Cross-link

107 ↔ 229

Tryptophyl-tyrosyl-methioninium (Trp-Tyr) (with M-255) HAMAP MF_01961

Cross-link

229 ↔ 255

Tryptophyl-tyrosyl-methioninium (Tyr-Met) (with W-107) HAMAP MF_01961

Natural variations

Natural variant

300

1

W → G in strain: H0892/92; INH-resistant.

Natural variant

315

1

S → T in strain: H0181/94, H0452/92, H0948/92 and H0169/93; INH-resistant. Ref.14

Natural variant

463

1

R → L in strain: H0169/93; INH-resistant.

Natural variant

501

1

P → A in strain: H0948/92; INH-resistant.

Natural variant

525

1

Q → P in strain: H0251/90; INH-resistant.

Natural variant

587

1

L → P in strain: 15726/89; INH-resistant.

Natural variant

700

1

S → P in strain: H0004/93; INH-resistant.

Experimental info

Sequence conflict

234

1

G → A in CAA48213. Ref.1

Secondary structure

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740

Helix Strand Turn

Details...

Helix

29 – 31

3

Helix

35 – 37

3

Helix

45 – 49

5

Helix

53 – 55

3

Helix

64 – 68

5

Helix

73 – 84

12

Helix

94 – 96

3

Helix

99 – 111

13

Turn

115 – 117

3

Helix

126 – 128

3

Helix

132 – 134

3

Helix

136 – 138

3

Helix

141 – 147

7

Helix

149 – 155

7

Helix

156 – 158

3

Helix

161 – 175

15

Turn

212 – 214

3

Beta strand

222 – 224

3

Beta strand

228 – 230

3

Helix

235 – 237

3

Helix

241 – 253

13

Turn

254 – 256

3

Helix

259 – 269

11

Beta strand

277 – 279

3

Helix

288 – 290

3

Helix

293 – 295

3

Helix

309 – 311

3

Beta strand

313 – 316

4

Helix

331 – 338

8

Beta strand

341 – 345

5

Beta strand

351 – 355

5

Helix

356 – 358

3

Beta strand

367 – 369

3

Helix

379 – 386

8

Helix

388 – 399

12

Helix

401 – 417

17

Helix

418 – 420

3

Helix

423 – 425

3

Helix

437 – 439

3

Helix

452 – 463

12

Helix

469 – 480

12

Turn

485 – 488

4

Helix

496 – 498

3

Helix

502 – 504

3

Helix

510 – 512

3

Helix

514 – 531

18

Beta strand

533 – 536

4

Helix

540 – 558

19

Helix

576 – 578

3

Helix

581 – 584

4

Helix

585 – 587

3

Beta strand

590 – 592

3

Helix

593 – 595

3

Helix

606 – 616

11

Helix

621 – 633

13

Helix

638 – 640

3

Helix

656 – 661

6

Beta strand

666 – 670

5

Beta strand

672 – 676

5

Beta strand

678 – 681

4

Beta strand

683 – 685

3

Beta strand

687 – 691

5

Helix

693 – 700

8

Helix

702 – 711

10

Helix

717 – 732

16

Turn

733 – 735

3

Helix

737 – 739

3

Sequences

	Sequence		Length	Mass (Da)
	Q08129-1 [UniParc]. Last modified May 30, 2000. Version 3. Checksum: B43C033B533CDD89	FASTA	740	80,605
	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

References

	« Hide 'large scale' referencesShow '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: 8320241] [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: 7798673] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 25618.
[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. , 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: 9634230] [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. , 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: 12218036] [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: 1501713] [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]	"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: 15840564] [Abstract] Cited for: COVALENT BOND.
[10]	"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: 17260948] [Abstract] Cited for: CATALYTIC MECHANISM.
[11]	"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: 18052167] [Abstract] Cited for: RADICAL INTERMEDIATE.
[12]	"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: 18178143] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
[13]	"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: 15231843] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.41 ANGSTROMS) OF 2-740.
[14]	"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: 16566587] [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

EMBLGenBankDDBJ

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.

PIR

A40662. A70519.

RefSeq

NP_216424.1.
NP_336417.1.

3D structure databases

PDBPDBe

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	[»]

ModBase

Search...

Protein family/group databases

PeroxiBase

3551. MtuCP01_H37rv.

Genome annotation databases

GeneID

885638.
923602.

GenomeReviews

Gene locus MT1959 in contig AE000516_GR.
Gene locus Rv1908c in contig AL123456_GR.

KEGG

mtc:MT1959.
mtu:Rv1908c.

TIGR

MT1959.

Organism-specific databases

TubercuList

Rv1908c.

Phylogenomic databases

OMA

KTGEPRW.

Enzyme and pathway databases

BRENDA

1.11.1.6. 809.

Family and domain databases

HAMAP

MF_01961.
[Tree]

InterPro

IPR000763. Catalase_proxase.
IPR002016. Haem_peroxidase_pln/fun/bac.
IPR019794. Peroxidases_AS.
IPR019793. Peroxidases_heam-ligand_BS.
[Graphical view]

Pfam

PF00141. peroxidase. 2 hits.
[Graphical view]

PRINTS

PR00460. BPEROXIDASE.
PR00458. PEROXIDASE.

TIGRFAMs

TIGR00198. cat_per_HPI. 1 hit.

PROSITE

PS00435. PEROXIDASE_1. 1 hit.
PS00436. PEROXIDASE_2. 1 hit.
PS50873. PEROXIDASE_4. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00609. Ethionamide.
DB00951. Isoniazid.

Entry information

Entry name

KATG_MYCTU

Accession

Primary (citable) accession number: Q08129
Secondary accession number(s): O08221 , Q50544, Q50546, Q50551, Q50552, Q50553, Q50554, Q50555, Q57215, Q57274

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	May 30, 2000
Last modified:	November 3, 2009
This is version 83 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HAMAP (High-quality Automated and Manual Annotation of microbial Proteomes)