ID   HDOX2_STAAN             Reviewed;         108 AA.
AC   Q7A827;
DT   09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   27-MAR-2024, entry version 113.
DE   RecName: Full=Heme oxygenase (staphylobilin-producing) 2 {ECO:0000255|HAMAP-Rule:MF_01272};
DE            EC=1.14.99.48 {ECO:0000255|HAMAP-Rule:MF_01272, ECO:0000269|PubMed:20180905};
DE   AltName: Full=Heme-degrading monooxygenase 2 {ECO:0000255|HAMAP-Rule:MF_01272};
DE   AltName: Full=Iron-regulated surface determinant 2 {ECO:0000255|HAMAP-Rule:MF_01272};
DE   AltName: Full=Iron-responsive surface determinant 2 {ECO:0000255|HAMAP-Rule:MF_01272};
GN   Name=isdI; OrderedLocusNames=SA0160;
OS   Staphylococcus aureus (strain N315).
OC   Bacteria; Bacillota; Bacilli; Bacillales; Staphylococcaceae;
OC   Staphylococcus.
OX   NCBI_TaxID=158879;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=N315;
RX   PubMed=11418146; DOI=10.1016/s0140-6736(00)04403-2;
RA   Kuroda M., Ohta T., Uchiyama I., Baba T., Yuzawa H., Kobayashi I., Cui L.,
RA   Oguchi A., Aoki K., Nagai Y., Lian J.-Q., Ito T., Kanamori M.,
RA   Matsumaru H., Maruyama A., Murakami H., Hosoyama A., Mizutani-Ui Y.,
RA   Takahashi N.K., Sawano T., Inoue R., Kaito C., Sekimizu K., Hirakawa H.,
RA   Kuhara S., Goto S., Yabuzaki J., Kanehisa M., Yamashita A., Oshima K.,
RA   Furuya K., Yoshino C., Shiba T., Hattori M., Ogasawara N., Hayashi H.,
RA   Hiramatsu K.;
RT   "Whole genome sequencing of meticillin-resistant Staphylococcus aureus.";
RL   Lancet 357:1225-1240(2001).
RN   [2]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   STRAIN=N315;
RA   Vaezzadeh A.R., Deshusses J., Lescuyer P., Hochstrasser D.F.;
RT   "Shotgun proteomic analysis of total and membrane protein extracts of S.
RT   aureus strain N315.";
RL   Submitted (OCT-2007) to UniProtKB.
RN   [3]
RP   X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 1-108 IN COMPLEX WITH HEME,
RP   FUNCTION, AND SUBUNIT.
RX   PubMed=18713745; DOI=10.1074/jbc.m709486200;
RA   Lee W.C., Reniere M.L., Skaar E.P., Murphy M.E.;
RT   "Ruffling of metalloporphyrins bound to IsdG and IsdI, two heme-degrading
RT   enzymes in Staphylococcus aureus.";
RL   J. Biol. Chem. 283:30957-30963(2008).
RN   [4]
RP   X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 1-108 IN COMPLEX WITH HEME,
RP   FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT.
RX   PubMed=20180905; DOI=10.1111/j.1365-2958.2010.07076.x;
RA   Reniere M.L., Ukpabi G.N., Harry S.R., Stec D.F., Krull R., Wright D.W.,
RA   Bachmann B.O., Murphy M.E., Skaar E.P.;
RT   "The IsdG-family of haem oxygenases degrades haem to a novel chromophore.";
RL   Mol. Microbiol. 75:1529-1538(2010).
RN   [5]
RP   X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 1-108 IN COMPLEX WITH HEME, AND
RP   SUBUNIT.
RA   Takayama S.J., Ukpabi G.N., Murphy M.E.P., Mauk A.G.;
RT   "Heme ruffling enables the catalytic activity of the heme degrading enzyme
RT   IsdI.";
RL   Submitted (JAN-2011) to the PDB data bank.
RN   [6]
RP   X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 1-108 OF MUTANT THR-66 IN COMPLEX
RP   WITH HEME, MUTAGENESIS OF TRP-66, AND SUBUNIT.
RX   PubMed=22891243; DOI=10.1074/jbc.m112.393249;
RA   Ukpabi G., Takayama S.J., Mauk A.G., Murphy M.E.;
RT   "Inactivation of the heme degrading enzyme IsdI by an active site
RT   substitution that diminishes heme ruffling.";
RL   J. Biol. Chem. 287:34179-34188(2012).
CC   -!- FUNCTION: Allows bacterial pathogens to use the host heme as an iron
CC       source. Catalyzes the oxidative degradation of the heme macrocyclic
CC       porphyrin ring to the oxo-bilirubin chromophore staphylobilin (a
CC       mixture of the linear tetrapyrroles 5-oxo-delta-bilirubin and 15-oxo-
CC       beta-bilirubin) 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:0000255|HAMAP-Rule:MF_01272,
CC       ECO:0000269|PubMed:18713745, ECO:0000269|PubMed:20180905}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=5 AH2 + 2 H(+) + heme b + 4 O2 = 5 A + delta-staphylobilin +
CC         Fe(2+) + formaldehyde + 4 H2O; Xref=Rhea:RHEA:37039,
CC         ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:16842, ChEBI:CHEBI:17499,
CC         ChEBI:CHEBI:29033, ChEBI:CHEBI:60344, ChEBI:CHEBI:74361;
CC         EC=1.14.99.48; Evidence={ECO:0000255|HAMAP-Rule:MF_01272,
CC         ECO:0000269|PubMed:20180905};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=5 AH2 + 2 H(+) + heme b + 4 O2 = 5 A + beta-staphylobilin +
CC         Fe(2+) + formaldehyde + 4 H2O; Xref=Rhea:RHEA:37363,
CC         ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:16842, ChEBI:CHEBI:17499,
CC         ChEBI:CHEBI:29033, ChEBI:CHEBI:60344, ChEBI:CHEBI:74362;
CC         EC=1.14.99.48; Evidence={ECO:0000255|HAMAP-Rule:MF_01272,
CC         ECO:0000269|PubMed:20180905};
CC   -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_01272,
CC       ECO:0000269|PubMed:18713745, ECO:0000269|PubMed:20180905,
CC       ECO:0000269|PubMed:22891243, ECO:0000269|Ref.5}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_01272}.
CC   -!- SIMILARITY: Belongs to the antibiotic biosynthesis monooxygenase
CC       family. Heme-degrading monooxygenase IsdG subfamily.
CC       {ECO:0000255|HAMAP-Rule:MF_01272}.
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DR   EMBL; BA000018; BAB41380.1; -; Genomic_DNA.
DR   PIR; A89778; A89778.
DR   RefSeq; WP_000480603.1; NC_002745.2.
DR   PDB; 2ZDP; X-ray; 1.50 A; A/B=1-108.
DR   PDB; 3LGM; X-ray; 1.88 A; A/B=1-108.
DR   PDB; 3LGN; X-ray; 1.50 A; A/B=1-108.
DR   PDB; 3QGP; X-ray; 1.80 A; A/B=1-108.
DR   PDB; 4FNH; X-ray; 1.90 A; A/B=1-108.
DR   PDB; 4FNI; X-ray; 1.80 A; A/B=1-108.
DR   PDBsum; 2ZDP; -.
DR   PDBsum; 3LGM; -.
DR   PDBsum; 3LGN; -.
DR   PDBsum; 3QGP; -.
DR   PDBsum; 4FNH; -.
DR   PDBsum; 4FNI; -.
DR   AlphaFoldDB; Q7A827; -.
DR   SMR; Q7A827; -.
DR   EnsemblBacteria; BAB41380; BAB41380; BAB41380.
DR   KEGG; sau:SA0160; -.
DR   HOGENOM; CLU_141544_2_1_9; -.
DR   BioCyc; MetaCyc:MONOMER-20095; -.
DR   BRENDA; 1.14.99.48; 3352.
DR   EvolutionaryTrace; Q7A827; -.
DR   Proteomes; UP000000751; Chromosome.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0020037; F:heme binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0004392; F:heme oxygenase (decyclizing) activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0005506; F:iron ion binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0042167; P:heme catabolic process; IEA:UniProtKB-UniRule.
DR   GO; GO:0033212; P:iron import into cell; IEA:InterPro.
DR   Gene3D; 3.30.70.100; -; 1.
DR   HAMAP; MF_01272; Heme_degrading_monooxygenase; 1.
DR   InterPro; IPR007138; ABM_dom.
DR   InterPro; IPR011008; Dimeric_a/b-barrel.
DR   InterPro; IPR023953; IsdG.
DR   PANTHER; PTHR34474:SF4; HEME OXYGENASE (STAPHYLOBILIN-PRODUCING) 1; 1.
DR   PANTHER; PTHR34474; SIGNAL TRANSDUCTION PROTEIN TRAP; 1.
DR   Pfam; PF03992; ABM; 1.
DR   SUPFAM; SSF54909; Dimeric alpha+beta barrel; 1.
DR   PROSITE; PS51725; ABM; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cytoplasm; Heme; Iron; Metal-binding; Monooxygenase;
KW   Oxidoreductase.
FT   CHAIN           1..108
FT                   /note="Heme oxygenase (staphylobilin-producing) 2"
FT                   /id="PRO_0000270092"
FT   DOMAIN          2..93
FT                   /note="ABM"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01272"
FT   BINDING         6
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT   BINDING         21..28
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT   BINDING         76
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   SITE            66
FT                   /note="Transition state stabilizer"
FT   MUTAGEN         66
FT                   /note="W->A: Inactive."
FT                   /evidence="ECO:0000269|PubMed:22891243"
FT   MUTAGEN         66
FT                   /note="W->F: Heme degradation activity is approximately
FT                   half that of the wild-type enzyme."
FT                   /evidence="ECO:0000269|PubMed:22891243"
FT   MUTAGEN         66
FT                   /note="W->L: Inactive."
FT                   /evidence="ECO:0000269|PubMed:22891243"
FT   MUTAGEN         66
FT                   /note="W->Y: Heme degradation activity is approximately
FT                   half that of the wild-type enzyme. Heme binds to this
FT                   enzyme with less heme ruffling than observed for
FT                   wild-type."
FT                   /evidence="ECO:0000269|PubMed:22891243"
FT   STRAND          2..10
FT                   /evidence="ECO:0007829|PDB:2ZDP"
FT   HELIX           15..20
FT                   /evidence="ECO:0007829|PDB:2ZDP"
FT   HELIX           21..23
FT                   /evidence="ECO:0007829|PDB:4FNH"
FT   HELIX           28..30
FT                   /evidence="ECO:0007829|PDB:2ZDP"
FT   STRAND          34..42
FT                   /evidence="ECO:0007829|PDB:2ZDP"
FT   STRAND          47..58
FT                   /evidence="ECO:0007829|PDB:2ZDP"
FT   HELIX           60..67
FT                   /evidence="ECO:0007829|PDB:2ZDP"
FT   HELIX           70..75
FT                   /evidence="ECO:0007829|PDB:2ZDP"
FT   TURN            76..78
FT                   /evidence="ECO:0007829|PDB:2ZDP"
FT   STRAND          92..107
FT                   /evidence="ECO:0007829|PDB:2ZDP"
SQ   SEQUENCE   108 AA;  12791 MW;  8AF2718571451004 CRC64;
     MFMAENRLQL QKGSAEETIE RFYNRQGIET IEGFQQMFVT KTLNTEDTDE VKILTIWESE
     DSFNNWLNSD VFKEAHKNVR LKSDDDGQQS PILSNKVFKY DIGYHYQK
//