MHUD_MYCTU
ID MHUD_MYCTU Reviewed; 105 AA.
AC P9WKH3; F2GKD2; O06156; Q7D578;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 38.
DE RecName: Full=Heme oxygenase (mycobilin-producing) {ECO:0000305};
DE EC=1.14.99.57 {ECO:0000269|PubMed:19917297, ECO:0000269|PubMed:23420845};
DE AltName: Full=Mycobacterial heme utilization, degrader;
DE Short=MHUD;
GN Name=mhuD; OrderedLocusNames=Rv3592;
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 [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 [2]
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 [3]
RP FUNCTION, CATALYTIC ACTIVITY, NMR; EPR AND RAMAN SPECTROMETRY, HEME
RP BINDING, AND MUTAGENESIS OF ASN-7 AND HIS-75.
RX PubMed=23420845; DOI=10.1074/jbc.m112.448399;
RA Nambu S., Matsui T., Goulding C.W., Takahashi S., Ikeda-Saito M.;
RT "A new way to degrade heme: the Mycobacterium tuberculosis enzyme MhuD
RT catalyzes heme degradation without generating CO.";
RL J. Biol. Chem. 288:10101-10109(2013).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEX WITH HEME, FUNCTION,
RP CATALYTIC ACTIVITY, SUBUNIT, AND NOMENCLATURE.
RX PubMed=19917297; DOI=10.1016/j.jmb.2009.11.025;
RA Chim N., Iniguez A., Nguyen T.Q., Goulding C.W.;
RT "Unusual diheme conformation of the heme-degrading protein from
RT Mycobacterium tuberculosis.";
RL J. Mol. Biol. 395:595-608(2010).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH HEME AND CYANIDE.
RX PubMed=24901029; DOI=10.1021/ic500033b;
RA Graves A.B., Morse R.P., Chao A., Iniguez A., Goulding C.W., Liptak M.D.;
RT "Crystallographic and spectroscopic insights into heme degradation by
RT Mycobacterium tuberculosis MhuD.";
RL Inorg. Chem. 53:5931-5940(2014).
CC -!- FUNCTION: Catalyzes the oxidative degradation of the heme macrocyclic
CC porphyrin ring in the presence of a suitable electron donor such as
CC ascorbate or NADPH--cytochrome P450 reductase, with subsequent release
CC of free iron. {ECO:0000269|PubMed:19917297,
CC ECO:0000269|PubMed:23420845}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3 AH2 + 2 H(+) + heme b + 3 O2 = 3 A + Fe(2+) + 3 H2O +
CC mycobilin a; Xref=Rhea:RHEA:52232, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:29033, ChEBI:CHEBI:60344,
CC ChEBI:CHEBI:136507; EC=1.14.99.57;
CC Evidence={ECO:0000269|PubMed:19917297, ECO:0000269|PubMed:23420845};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3 AH2 + 2 H(+) + heme b + 3 O2 = 3 A + Fe(2+) + 3 H2O +
CC mycobilin b; Xref=Rhea:RHEA:52236, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:29033, ChEBI:CHEBI:60344,
CC ChEBI:CHEBI:136508; EC=1.14.99.57;
CC Evidence={ECO:0000269|PubMed:19917297, ECO:0000269|PubMed:23420845};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:19917297}.
CC -!- MISCELLANEOUS: MhuD has the ability to bind 2 heme molecules per
CC monomer but only the monoheme-protein complex is active.
CC {ECO:0000269|PubMed:23420845, ECO:0000305|PubMed:19917297}.
CC -!- SIMILARITY: Belongs to the antibiotic biosynthesis monooxygenase
CC family. {ECO:0000305}.
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DR EMBL; AL123456; CCP46415.1; -; Genomic_DNA.
DR PIR; E70552; E70552.
DR RefSeq; NP_218109.1; NC_000962.3.
DR RefSeq; WP_003419501.1; NZ_NVQJ01000092.1.
DR PDB; 3HX9; X-ray; 1.75 A; A/B=1-105.
DR PDB; 4NL5; X-ray; 1.90 A; A/B=1-105.
DR PDB; 5UQ4; X-ray; 2.20 A; A/B=1-105.
DR PDB; 6DS7; X-ray; 1.90 A; A/B=2-100.
DR PDB; 6DS8; X-ray; 2.40 A; A/B=2-100.
DR PDB; 6PLE; X-ray; 2.50 A; A/B=1-105.
DR PDBsum; 3HX9; -.
DR PDBsum; 4NL5; -.
DR PDBsum; 5UQ4; -.
DR PDBsum; 6DS7; -.
DR PDBsum; 6DS8; -.
DR PDBsum; 6PLE; -.
DR AlphaFoldDB; P9WKH3; -.
DR SMR; P9WKH3; -.
DR STRING; 83332.Rv3592; -.
DR PaxDb; P9WKH3; -.
DR DNASU; 886278; -.
DR GeneID; 45427579; -.
DR GeneID; 886278; -.
DR KEGG; mtu:Rv3592; -.
DR TubercuList; Rv3592; -.
DR eggNOG; COG2329; Bacteria.
DR OMA; VVTQWES; -.
DR PhylomeDB; P9WKH3; -.
DR BioCyc; MetaCyc:G185E-7870-MON; -.
DR BRENDA; 1.14.99.57; 3445.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0020037; F:heme binding; IDA:MTBBASE.
DR GO; GO:0004392; F:heme oxygenase (decyclizing) activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042167; P:heme catabolic process; IDA:MTBBASE.
DR InterPro; IPR007138; ABM_dom.
DR InterPro; IPR011008; Dimeric_a/b-barrel.
DR Pfam; PF03992; ABM; 1.
DR SUPFAM; SSF54909; SSF54909; 1.
DR PROSITE; PS51725; ABM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Heme; Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..105
FT /note="Heme oxygenase (mycobilin-producing)"
FT /id="PRO_0000422665"
FT DOMAIN 3..92
FT /note="ABM"
FT BINDING 22..26
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT BINDING 75
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT BINDING 83..86
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT SITE 66
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000255"
FT MUTAGEN 7
FT /note="N->A: Inactive."
FT /evidence="ECO:0000269|PubMed:23420845"
FT MUTAGEN 75
FT /note="H->A: Inactive."
FT /evidence="ECO:0000269|PubMed:23420845"
FT STRAND 3..9
FT /evidence="ECO:0007829|PDB:3HX9"
FT HELIX 16..25
FT /evidence="ECO:0007829|PDB:3HX9"
FT TURN 26..32
FT /evidence="ECO:0007829|PDB:3HX9"
FT STRAND 36..47
FT /evidence="ECO:0007829|PDB:3HX9"
FT STRAND 50..58
FT /evidence="ECO:0007829|PDB:3HX9"
FT HELIX 60..68
FT /evidence="ECO:0007829|PDB:3HX9"
FT HELIX 70..73
FT /evidence="ECO:0007829|PDB:3HX9"
FT TURN 74..77
FT /evidence="ECO:0007829|PDB:3HX9"
FT STRAND 87..100
FT /evidence="ECO:0007829|PDB:3HX9"
SQ SEQUENCE 105 AA; 11185 MW; 19CF8FA845269878 CRC64;
MPVVKINAIE VPAGAGPELE KRFAHRAHAV ENSPGFLGFQ LLRPVKGEER YFVVTHWESD
EAFQAWANGP AIAAHAGHRA NPVATGASLL EFEVVLDVGG TGKTA
