CPFC_MYCTU
ID CPFC_MYCTU Reviewed; 344 AA.
AC P9WNE3; L0T8E3; P0A576; P71765;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 42.
DE RecName: Full=Coproporphyrin III ferrochelatase {ECO:0000255|HAMAP-Rule:MF_00323, ECO:0000305};
DE EC=4.99.1.9 {ECO:0000255|HAMAP-Rule:MF_00323, ECO:0000269|PubMed:25646457};
GN Name=cpfC {ECO:0000255|HAMAP-Rule:MF_00323, ECO:0000303|PubMed:28123057};
GN Synonyms=hemH {ECO:0000303|PubMed:25646457},
GN hemZ {ECO:0000303|PubMed:15850757}; OrderedLocusNames=Rv1485;
GN ORFNames=MTCY277.06;
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 FUNCTION, COFACTOR, AND SUBUNIT.
RX PubMed=11948160; DOI=10.1128/jb.184.9.2460-2464.2002;
RA Dailey T.A., Dailey H.A.;
RT "Identification of [2Fe-2S] clusters in microbial ferrochelatases.";
RL J. Bacteriol. 184:2460-2464(2002).
RN [3]
RP PATHWAY.
RX PubMed=15850757; DOI=10.1016/j.tube.2005.01.002;
RA Parish T., Schaeffer M., Roberts G., Duncan K.;
RT "HemZ is essential for heme biosynthesis in Mycobacterium tuberculosis.";
RL Tuberculosis 85:197-204(2005).
RN [4]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [5]
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 [6]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RX PubMed=25646457; DOI=10.1073/pnas.1416285112;
RA Dailey H.A., Gerdes S., Dailey T.A., Burch J.S., Phillips J.D.;
RT "Noncanonical coproporphyrin-dependent bacterial heme biosynthesis pathway
RT that does not use protoporphyrin.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:2210-2215(2015).
RN [7]
RP PATHWAY, AND REVIEW.
RX PubMed=25711532; DOI=10.1016/j.abb.2015.02.017;
RA Dailey H.A., Gerdes S.;
RT "HemQ: An iron-coproporphyrin oxidative decarboxylase for protoheme
RT synthesis in Firmicutes and Actinobacteria.";
RL Arch. Biochem. Biophys. 574:27-35(2015).
RN [8]
RP NOMENCLATURE, AND REVIEW.
RX PubMed=28123057; DOI=10.1128/mmbr.00048-16;
RA Dailey H.A., Dailey T.A., Gerdes S., Jahn D., Jahn M., O'Brian M.R.,
RA Warren M.J.;
RT "Prokaryotic heme biosynthesis: multiple pathways to a common essential
RT product.";
RL Microbiol. Mol. Biol. Rev. 81:e00048-e00048(2017).
CC -!- FUNCTION: Involved in coproporphyrin-dependent heme b biosynthesis
CC (PubMed:25646457). Catalyzes the insertion of ferrous iron into
CC coproporphyrin III to form Fe-coproporphyrin III (PubMed:25646457). Has
CC weaker activity with coproporphyrin I, protoporphyrin IX,
CC deuteroporphyrin, 2,4 hydroxyethyl and 2,4 disulfonate
CC (PubMed:25646457, PubMed:11948160). {ECO:0000269|PubMed:11948160,
CC ECO:0000269|PubMed:25646457}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Fe-coproporphyrin III + 2 H(+) = coproporphyrin III + Fe(2+);
CC Xref=Rhea:RHEA:49572, ChEBI:CHEBI:15378, ChEBI:CHEBI:29033,
CC ChEBI:CHEBI:68438, ChEBI:CHEBI:131725; EC=4.99.1.9;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00323,
CC ECO:0000269|PubMed:25646457};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:49574;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00323,
CC ECO:0000269|PubMed:25646457};
CC -!- COFACTOR:
CC Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135;
CC Evidence={ECO:0000269|PubMed:11948160};
CC Note=Binds 1 [2Fe-2S] cluster. {ECO:0000269|PubMed:11948160};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=10.5 uM for coproporphyrin III {ECO:0000269|PubMed:25646457};
CC KM=720 uM for protoporphyrin IX {ECO:0000269|PubMed:25646457};
CC Note=kcat is 1.8 min(-1) with coproporphyrin III as substrate. kcat
CC is 0.8 min(-1) with protoporphyrin IX as substrate.
CC {ECO:0000269|PubMed:25646457};
CC -!- PATHWAY: Porphyrin-containing compound metabolism; protoheme
CC biosynthesis. {ECO:0000255|HAMAP-Rule:MF_00323,
CC ECO:0000269|PubMed:15850757, ECO:0000269|PubMed:25646457,
CC ECO:0000305|PubMed:25711532}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:11948160}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00323}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000269|PubMed:19099550}.
CC -!- SIMILARITY: Belongs to the ferrochelatase family. {ECO:0000255|HAMAP-
CC Rule:MF_00323, ECO:0000305}.
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DR EMBL; AL123456; CCP44245.1; -; Genomic_DNA.
DR PIR; H70710; H70710.
DR RefSeq; NP_216001.1; NC_000962.3.
DR RefSeq; WP_003407559.1; NZ_NVQJ01000004.1.
DR AlphaFoldDB; P9WNE3; -.
DR SMR; P9WNE3; -.
DR STRING; 83332.Rv1485; -.
DR PaxDb; P9WNE3; -.
DR DNASU; 886525; -.
DR GeneID; 45425464; -.
DR GeneID; 886525; -.
DR KEGG; mtu:Rv1485; -.
DR TubercuList; Rv1485; -.
DR eggNOG; COG0276; Bacteria.
DR OMA; WLEPDIC; -.
DR PhylomeDB; P9WNE3; -.
DR UniPathway; UPA00252; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; IDA:MTBBASE.
DR GO; GO:0004325; F:ferrochelatase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006783; P:heme biosynthetic process; IMP:MTBBASE.
DR CDD; cd00419; Ferrochelatase_C; 1.
DR CDD; cd03411; Ferrochelatase_N; 1.
DR HAMAP; MF_00323; Ferrochelatase; 1.
DR InterPro; IPR001015; Ferrochelatase.
DR InterPro; IPR019772; Ferrochelatase_AS.
DR InterPro; IPR033644; Ferrochelatase_C.
DR InterPro; IPR033659; Ferrochelatase_N.
DR PANTHER; PTHR11108; PTHR11108; 1.
DR Pfam; PF00762; Ferrochelatase; 1.
DR TIGRFAMs; TIGR00109; hemH; 1.
DR PROSITE; PS00534; FERROCHELATASE; 1.
PE 1: Evidence at protein level;
KW 2Fe-2S; Cytoplasm; Heme biosynthesis; Iron; Iron-sulfur; Lyase;
KW Metal-binding; Porphyrin biosynthesis; Reference proteome.
FT CHAIN 1..344
FT /note="Coproporphyrin III ferrochelatase"
FT /id="PRO_0000175167"
FT BINDING 52
FT /ligand="Fe-coproporphyrin III"
FT /ligand_id="ChEBI:CHEBI:68438"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00323"
FT BINDING 113
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000305|PubMed:11948160"
FT BINDING 116
FT /ligand="Fe-coproporphyrin III"
FT /ligand_id="ChEBI:CHEBI:68438"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00323"
FT BINDING 172
FT /ligand="Fe(2+)"
FT /ligand_id="ChEBI:CHEBI:29033"
FT /evidence="ECO:0000250|UniProtKB:P32396, ECO:0000255|HAMAP-
FT Rule:MF_00323"
FT BINDING 255
FT /ligand="Fe(2+)"
FT /ligand_id="ChEBI:CHEBI:29033"
FT /evidence="ECO:0000250|UniProtKB:P32396, ECO:0000255|HAMAP-
FT Rule:MF_00323"
FT BINDING 316
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000305|PubMed:11948160"
FT BINDING 325
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000305|PubMed:11948160"
FT BINDING 330
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /evidence="ECO:0000305|PubMed:11948160"
SQ SEQUENCE 344 AA; 37144 MW; 17A5023246B670B6 CRC64;
MQFDAVLLLS FGGPEGPEQV RPFLENVTRG RGVPAERLDA VAEHYLHFGG VSPINGINRT
LIAELEAQQE LPVYFGNRNW EPYVEDAVTA MRDNGVRRAA VFATSAWSGY SSCTQYVEDI
ARARRAAGRD APELVKLRPY FDHPLFVEMF ADAITAAAAT VRGDARLVFT AHSIPTAADR
RCGPNLYSRQ VAYATRLVAA AAGYCDFDLA WQSRSGPPQV PWLEPDVTDQ LTGLAGAGIN
AVIVCPIGFV ADHIEVVWDL DHELRLQAEA AGIAYARAST PNADPRFARL ARGLIDELRY
GRIPARVSGP DPVPGCLSSI NGQPCRPPHC VASVSPARPS AGSP
