HUTZ_VIBCH
ID HUTZ_VIBCH Reviewed; 176 AA.
AC Q9KL41;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 96.
DE RecName: Full=Heme oxygenase HutZ {ECO:0000305};
DE EC=1.14.99.58 {ECO:0000269|PubMed:28607990};
DE AltName: Full=Heme-degrading enzyme HutZ {ECO:0000303|PubMed:22627893};
GN Name=hutZ {ECO:0000303|PubMed:15205415};
GN OrderedLocusNames=VC_A0907 {ECO:0000312|EMBL:AAF96804.1};
OS Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Vibrionales; Vibrionaceae;
OC Vibrio.
OX NCBI_TaxID=243277;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 39315 / El Tor Inaba N16961;
RX PubMed=10952301; DOI=10.1038/35020000;
RA Heidelberg J.F., Eisen J.A., Nelson W.C., Clayton R.A., Gwinn M.L.,
RA Dodson R.J., Haft D.H., Hickey E.K., Peterson J.D., Umayam L.A., Gill S.R.,
RA Nelson K.E., Read T.D., Tettelin H., Richardson D.L., Ermolaeva M.D.,
RA Vamathevan J.J., Bass S., Qin H., Dragoi I., Sellers P., McDonald L.A.,
RA Utterback T.R., Fleischmann R.D., Nierman W.C., White O., Salzberg S.L.,
RA Smith H.O., Colwell R.R., Mekalanos J.J., Venter J.C., Fraser C.M.;
RT "DNA sequence of both chromosomes of the cholera pathogen Vibrio
RT cholerae.";
RL Nature 406:477-483(2000).
RN [2]
RP FUNCTION, HEME-BINDING, INDUCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=El Tor Lou15;
RX PubMed=15205415; DOI=10.1128/jb.186.13.4142-4151.2004;
RA Wyckoff E.E., Schmitt M., Wilks A., Payne S.M.;
RT "HutZ is required for efficient heme utilization in Vibrio cholerae.";
RL J. Bacteriol. 186:4142-4151(2004).
RN [3]
RP FUNCTION IN HEME DEGRADATION, HEME-BINDING, AND SUBUNIT.
RX PubMed=22627893; DOI=10.1039/c2cc31147j;
RA Uchida T., Sekine Y., Matsui T., Ikeda-Saito M., Ishimori K.;
RT "A heme degradation enzyme, HutZ, from Vibrio cholerae.";
RL Chem. Commun. (Camb.) 48:6741-6743(2012).
RN [4]
RP INTERACTION WITH HUTX.
RX PubMed=26807477; DOI=10.1021/acs.biochem.5b01273;
RA Sekine Y., Tanzawa T., Tanaka Y., Ishimori K., Uchida T.;
RT "Cytoplasmic heme-binding protein (HutX) from Vibrio cholerae is an
RT intracellular heme transport protein for the heme-degrading enzyme, HutZ.";
RL Biochemistry 55:884-893(2016).
RN [5]
RP FUNCTION, ACTIVITY REGULATION, HEME-BINDING, AND MUTAGENESIS OF HIS-63;
RP ASP-132 AND HIS-170.
RX PubMed=28481076; DOI=10.1021/acs.biochem.7b00152;
RA Uchida T., Dojun N., Sekine Y., Ishimori K.;
RT "Heme proximal hydrogen bonding between His170 and Asp132 plays an
RT essential role in the heme degradation reaction of HutZ from Vibrio
RT cholerae.";
RL Biochemistry 56:2723-2734(2017).
RN [6]
RP ACTIVITY REGULATION, AND MUTAGENESIS OF THR-27.
RX PubMed=28352909; DOI=10.1039/c7dt00121e;
RA Dojun N., Sekine Y., Ishimori K., Uchida T.;
RT "Iron chelators inhibit the heme-degradation reaction by HutZ from Vibrio
RT cholerae.";
RL Dalton Trans. 46:5147-5150(2017).
RN [7]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=28607990; DOI=10.1039/c7dt01562c;
RA Uchida T., Sekine Y., Dojun N., Lewis-Ballester A., Ishigami I., Matsui T.,
RA Yeh S.R., Ishimori K.;
RT "Reaction intermediates in the heme degradation reaction by HutZ from
RT Vibrio cholerae.";
RL Dalton Trans. 46:8104-8109(2017).
RN [8] {ECO:0007744|PDB:3TGV}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 13-150, AND SUBUNIT.
RC STRAIN=ATCC 39315 / El Tor Inaba N16961;
RX PubMed=23013214; DOI=10.1186/1472-6807-12-23;
RA Liu X., Gong J., Wei T., Wang Z., Du Q., Zhu D., Huang Y., Xu S., Gu L.;
RT "Crystal structure of HutZ, a heme storage protein from Vibrio cholerae: A
RT structural mismatch observed in the region of high sequence conservation.";
RL BMC Struct. Biol. 12:23-23(2012).
CC -!- FUNCTION: Involved in heme degradation (PubMed:15205415,
CC PubMed:22627893, PubMed:28481076, PubMed:28607990). Catalyzes the
CC degradation of heme to biliverdin, with the release of iron
CC (PubMed:22627893, PubMed:28607990). Forms biliverdin beta and delta
CC (PubMed:28607990). Binds heme with high efficiency (PubMed:15205415,
CC PubMed:22627893). {ECO:0000269|PubMed:15205415,
CC ECO:0000269|PubMed:22627893, ECO:0000269|PubMed:28481076,
CC ECO:0000269|PubMed:28607990}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3 AH2 + 2 H(+) + heme b + 3 O2 = 3 A + biliverdin beta + CO +
CC Fe(2+) + 3 H2O; Xref=Rhea:RHEA:52228, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17245, ChEBI:CHEBI:17499, ChEBI:CHEBI:29033,
CC ChEBI:CHEBI:60344, ChEBI:CHEBI:136509; EC=1.14.99.58;
CC Evidence={ECO:0000269|PubMed:28607990};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3 AH2 + 3 H(+) + heme b + 3 O2 = 3 A + biliverdin delta + CO +
CC Fe(2+) + 3 H2O; Xref=Rhea:RHEA:52224, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17245, ChEBI:CHEBI:17499, ChEBI:CHEBI:29033,
CC ChEBI:CHEBI:60344, ChEBI:CHEBI:136510; EC=1.14.99.58;
CC Evidence={ECO:0000269|PubMed:28607990};
CC -!- ACTIVITY REGULATION: Activity is pH-dependent. A proximal hydrogen bond
CC between Asp-132 and the heme axial ligant His-170 is essential for heme
CC degradation activity (PubMed:28481076). Heme-degradation reaction is
CC inhibited by iron chelators (PubMed:28352909).
CC {ECO:0000269|PubMed:28352909, ECO:0000269|PubMed:28481076}.
CC -!- SUBUNIT: Homodimer (PubMed:22627893, PubMed:23013214). Interacts with
CC HutX, leading to the transfer of the heme from HutX to apo-HutZ
CC (PubMed:26807477). {ECO:0000269|PubMed:22627893,
CC ECO:0000269|PubMed:23013214, ECO:0000269|PubMed:26807477}.
CC -!- INDUCTION: Negatively regulated by iron. {ECO:0000269|PubMed:15205415}.
CC -!- DISRUPTION PHENOTYPE: Mutant is defective in heme utilization.
CC {ECO:0000269|PubMed:15205415}.
CC -!- SIMILARITY: Belongs to the heme oxygenase HugZ/HutZ family.
CC {ECO:0000305}.
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DR EMBL; AE003853; AAF96804.1; -; Genomic_DNA.
DR PIR; A82403; A82403.
DR RefSeq; NP_233292.1; NC_002506.1.
DR RefSeq; WP_000372763.1; NZ_LT906615.1.
DR PDB; 3TGV; X-ray; 2.00 A; A/B/C/D=13-150.
DR PDBsum; 3TGV; -.
DR AlphaFoldDB; Q9KL41; -.
DR SMR; Q9KL41; -.
DR STRING; 243277.VC_A0907; -.
DR PRIDE; Q9KL41; -.
DR DNASU; 2612246; -.
DR EnsemblBacteria; AAF96804; AAF96804; VC_A0907.
DR GeneID; 66941036; -.
DR KEGG; vch:VC_A0907; -.
DR PATRIC; fig|243277.26.peg.3522; -.
DR eggNOG; COG0748; Bacteria.
DR HOGENOM; CLU_093808_1_0_6; -.
DR OMA; QERRTLQ; -.
DR BioCyc; VCHO:VCA0907-MON; -.
DR Proteomes; UP000000584; Chromosome 2.
DR GO; GO:0070967; F:coenzyme F420 binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016627; F:oxidoreductase activity, acting on the CH-CH group of donors; IBA:GO_Central.
DR Gene3D; 2.30.110.10; -; 1.
DR InterPro; IPR014419; HutZ.
DR InterPro; IPR011576; Pyridox_Oxase_put.
DR InterPro; IPR012349; Split_barrel_FMN-bd.
DR Pfam; PF01243; Putative_PNPOx; 1.
DR PIRSF; PIRSF004633; UCP_PLP_oxd; 1.
DR TIGRFAMs; TIGR04110; heme_HutZ; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Heme; Iron; Metal-binding; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..176
FT /note="Heme oxygenase HutZ"
FT /id="PRO_0000446445"
FT BINDING 170
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 /evidence="ECO:0000305|PubMed:28481076"
FT SITE 132
FT /note="Important for activity"
FT /evidence="ECO:0000305|PubMed:28481076"
FT MUTAGEN 27
FT /note="T->V: 2-fold decrease in the amount of liberated
FT Fe(2+)."
FT /evidence="ECO:0000269|PubMed:28352909"
FT MUTAGEN 63
FT /note="H->L: Cannot bind heme; when associated with A-170."
FT /evidence="ECO:0000269|PubMed:28481076"
FT MUTAGEN 132
FT /note="D->E: At pH 8.0, does not affect heme affinity and
FT activity. At pH 6.0, shows a significant reduction in
FT affinity for heme."
FT /evidence="ECO:0000269|PubMed:28481076"
FT MUTAGEN 132
FT /note="D->L,N: At pH 8.0, slight decrease in heme affinity.
FT Almost complete loss of heme degradation activity."
FT /evidence="ECO:0000269|PubMed:28481076"
FT MUTAGEN 170
FT /note="H->A: Can still bind heme. Retains heme degradation
FT activity, but it eliminates pH-dependent activation. Cannot
FT bind heme; when associated with L-63."
FT /evidence="ECO:0000269|PubMed:28481076"
SQ SEQUENCE 176 AA; 20300 MW; 361E569BF68A0A9A CRC64;
MDQQVKQERL QGRLEPEIKE FRQERKTLQL ATVDAQGRPN VSYAPFVQNQ EGYFVLISHI
ARHARNLEVN PQVSIMMIED ETEAKQLFAR KRLTFDAVAS MVERDSELWC QVIAQMGERF
GEIIDGLSQL QDFMLFRLQP EQGLFVKGFG QAYQVSGDDL VDFVHLEEGH RKISNG
