HEM3_ECOLI
ID HEM3_ECOLI Reviewed; 313 AA.
AC P06983; P78125; Q2M8B0;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Porphobilinogen deaminase;
DE Short=PBG;
DE EC=2.5.1.61 {ECO:0000269|PubMed:3052434};
DE AltName: Full=Hydroxymethylbilane synthase;
DE Short=HMBS;
DE AltName: Full=Pre-uroporphyrinogen synthase;
GN Name=hemC; Synonyms=popE; OrderedLocusNames=b3805, JW5932;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-6, FUNCTION, AND
RP SUBUNIT.
RC STRAIN=K12;
RX PubMed=3529035; DOI=10.1093/nar/14.15.6215;
RA Thomas S.D., Jordan P.M.;
RT "Nucleotide sequence of the hemC locus encoding porphobilinogen deaminase
RT of Escherichia coli K12.";
RL Nucleic Acids Res. 14:6215-6226(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12 / CS520;
RX PubMed=3054815; DOI=10.1093/nar/16.20.9871;
RA Alefounder P.R., Abell C., Battersby A.R.;
RT "The sequence of hemC, hemD and two additional E. coli genes.";
RL Nucleic Acids Res. 16:9871-9871(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=1379743; DOI=10.1126/science.1379743;
RA Daniels D.L., Plunkett G. III, Burland V.D., Blattner F.R.;
RT "Analysis of the Escherichia coli genome: DNA sequence of the region from
RT 84.5 to 86.5 minutes.";
RL Science 257:771-778(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND SEQUENCE REVISION TO
RP 137.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [5]
RP SEQUENCE REVISION TO 186 AND 265.
RX PubMed=16397293; DOI=10.1093/nar/gkj405;
RA Riley M., Abe T., Arnaud M.B., Berlyn M.K.B., Blattner F.R.,
RA Chaudhuri R.R., Glasner J.D., Horiuchi T., Keseler I.M., Kosuge T.,
RA Mori H., Perna N.T., Plunkett G. III, Rudd K.E., Serres M.H., Thomas G.H.,
RA Thomson N.R., Wishart D., Wanner B.L.;
RT "Escherichia coli K-12: a cooperatively developed annotation snapshot
RT -- 2005.";
RL Nucleic Acids Res. 34:1-9(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-89.
RC STRAIN=K12;
RX PubMed=8874804; DOI=10.1016/0300-9084(96)82192-4;
RA Trotot P., Sismeiro O., Vivares C., Glaser P., Bresson-Roy A., Danchin A.;
RT "Comparative analysis of the cya locus in enterobacteria and related Gram-
RT negative facultative anaerobes.";
RL Biochimie 78:277-287(1996).
RN [8]
RP PROTEIN SEQUENCE OF 1-10, AND CATALYTIC ACTIVITY.
RX PubMed=3052434; DOI=10.1042/bj2540427;
RA Jordan P.M., Thomas S.D., Warren M.J.;
RT "Purification, crystallization and properties of porphobilinogen deaminase
RT from a recombinant strain of Escherichia coli K12.";
RL Biochem. J. 254:427-435(1988).
RN [9]
RP PROSTHETIC GROUP AT CYS-242.
RX PubMed=3196304; DOI=10.1042/bj2540915;
RA Miller A.D., Hart G.J., Packman L.C., Battersby A.R.;
RT "Evidence that the pyrromethane cofactor of hydroxymethylbilane synthase
RT (porphobilinogen deaminase) is bound to the protein through the sulphur
RT atom of cysteine-242.";
RL Biochem. J. 254:915-918(1988).
RN [10]
RP INACTIVATION BY PYRIDOXAL 5'-PHOSPHATE.
RX PubMed=2510713; DOI=10.1042/bj2620119;
RA Miller A.D., Packman L.C., Hart G.J., Alefounder P.R., Abell C.,
RA Battersby A.R.;
RT "Evidence that pyridoxal phosphate modification of lysine residues (Lys-55
RT and Lys-59) causes inactivation of hydroxymethylbilane synthase
RT (porphobilinogen deaminase).";
RL Biochem. J. 262:119-124(1989).
RN [11]
RP MUTAGENESIS OF LYS-55 AND LYS-59.
RX PubMed=2122889; DOI=10.1042/bj2710487;
RA Hadener A., Alefounder P.R., Hart G.J., Abell C., Battersby A.R.;
RT "Investigation of putative active-site lysine residues in
RT hydroxymethylbilane synthase. Preparation and characterization of mutants
RT in which (a) Lys-55, (b) Lys-59 and (c) both Lys-55 and Lys-59 have been
RT replaced by glutamine.";
RL Biochem. J. 271:487-491(1990).
RN [12]
RP MUTAGENESIS OF ARGININE RESIDUES.
RX PubMed=2025226; DOI=10.1042/bj2750447;
RA Lander M., Pitt A.R., Alefounder P.R., Bardy D., Abell C., Battersby A.R.;
RT "Studies on the mechanism of hydroxymethylbilane synthase concerning the
RT role of arginine residues in substrate binding.";
RL Biochem. J. 275:447-452(1991).
RN [13]
RP MUTAGENESIS OF ARGININE RESIDUES.
RX PubMed=1747120; DOI=10.1042/bj2800445;
RA Jordan P.M., Woodcock S.C.;
RT "Mutagenesis of arginine residues in the catalytic cleft of Escherichia
RT coli porphobilinogen deaminase that affects dipyrromethane cofactor
RT assembly and tetrapyrrole chain initiation and elongation.";
RL Biochem. J. 280:445-449(1991).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS), AND PROSTHETIC GROUP AT CYS-242.
RX PubMed=1522882; DOI=10.1038/359033a0;
RA Louie G.V., Brownlie P.D., Labert R., Cooper J.B., Blundell T.L.,
RA Wood S.P., Warren M.J., Woodcock S.C., Jordan P.M.;
RT "Structure of porphobilinogen deaminase reveals a flexible multidomain
RT polymerase with a single catalytic site.";
RL Nature 359:33-39(1992).
CC -!- FUNCTION: Tetrapolymerization of the monopyrrole PBG into the
CC hydroxymethylbilane pre-uroporphyrinogen in several discrete steps.
CC {ECO:0000269|PubMed:3529035}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + 4 porphobilinogen = hydroxymethylbilane + 4 NH4(+);
CC Xref=Rhea:RHEA:13185, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:57845, ChEBI:CHEBI:58126; EC=2.5.1.61;
CC Evidence={ECO:0000269|PubMed:3052434};
CC -!- COFACTOR:
CC Name=dipyrromethane; Xref=ChEBI:CHEBI:60342;
CC Note=Binds 1 dipyrromethane group covalently.;
CC -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX
CC biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 2/4.
CC {ECO:0000305|PubMed:3052434}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:3529035}.
CC -!- MISCELLANEOUS: Arginine residues that are closely associated with one
CC another might be involved in substrate binding.
CC -!- MISCELLANEOUS: The porphobilinogen subunits are added to the
CC dipyrromethane group.
CC -!- SIMILARITY: Belongs to the HMBS family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA67601.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; X04242; CAA27813.1; -; Genomic_DNA.
DR EMBL; X12614; CAA31132.1; -; Genomic_DNA.
DR EMBL; M87049; AAA67601.1; ALT_INIT; Genomic_DNA.
DR EMBL; U00096; AAT48218.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE77496.1; -; Genomic_DNA.
DR EMBL; X66782; CAA47279.1; -; Genomic_DNA.
DR PIR; F65184; IBEC.
DR RefSeq; WP_001338644.1; NZ_SSZK01000025.1.
DR RefSeq; YP_026260.1; NC_000913.3.
DR PDB; 1AH5; X-ray; 2.40 A; A=1-313.
DR PDB; 1GTK; X-ray; 1.66 A; A=1-313.
DR PDB; 1PDA; X-ray; 1.76 A; A=1-313.
DR PDB; 1YPN; X-ray; 2.30 A; A=1-313.
DR PDB; 2YPN; X-ray; 2.30 A; A=1-313.
DR PDBsum; 1AH5; -.
DR PDBsum; 1GTK; -.
DR PDBsum; 1PDA; -.
DR PDBsum; 1YPN; -.
DR PDBsum; 2YPN; -.
DR AlphaFoldDB; P06983; -.
DR SMR; P06983; -.
DR BioGRID; 4259657; 9.
DR DIP; DIP-9879N; -.
DR IntAct; P06983; 1.
DR STRING; 511145.b3805; -.
DR DrugBank; DB04517; Dipyrromethane Cofactor.
DR jPOST; P06983; -.
DR PaxDb; P06983; -.
DR PRIDE; P06983; -.
DR EnsemblBacteria; AAT48218; AAT48218; b3805.
DR EnsemblBacteria; BAE77496; BAE77496; BAE77496.
DR GeneID; 947759; -.
DR KEGG; ecj:JW5932; -.
DR KEGG; eco:b3805; -.
DR PATRIC; fig|511145.12.peg.3920; -.
DR EchoBASE; EB0424; -.
DR eggNOG; COG0181; Bacteria.
DR HOGENOM; CLU_019704_0_2_6; -.
DR InParanoid; P06983; -.
DR OMA; LWQANHI; -.
DR PhylomeDB; P06983; -.
DR BioCyc; EcoCyc:OHMETHYLBILANESYN-MON; -.
DR BioCyc; MetaCyc:OHMETHYLBILANESYN-MON; -.
DR BRENDA; 2.5.1.61; 2026.
DR UniPathway; UPA00251; UER00319.
DR EvolutionaryTrace; P06983; -.
DR PRO; PR:P06983; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IDA:EcoliWiki.
DR GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR GO; GO:0004418; F:hydroxymethylbilane synthase activity; IDA:EcoCyc.
DR GO; GO:0006783; P:heme biosynthetic process; IMP:EcoliWiki.
DR GO; GO:0018160; P:peptidyl-pyrromethane cofactor linkage; IDA:EcoliWiki.
DR GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IDA:EcoCyc.
DR GO; GO:0033014; P:tetrapyrrole biosynthetic process; IMP:EcoliWiki.
DR Gene3D; 3.30.160.40; -; 1.
DR HAMAP; MF_00260; Porphobil_deam; 1.
DR InterPro; IPR000860; HemC.
DR InterPro; IPR022419; Porphobilin_deaminase_cofac_BS.
DR InterPro; IPR022417; Porphobilin_deaminase_N.
DR InterPro; IPR022418; Porphobilinogen_deaminase_C.
DR InterPro; IPR036803; Porphobilinogen_deaminase_C_sf.
DR PANTHER; PTHR11557; PTHR11557; 1.
DR Pfam; PF01379; Porphobil_deam; 1.
DR Pfam; PF03900; Porphobil_deamC; 1.
DR PIRSF; PIRSF001438; 4pyrrol_synth_OHMeBilane_synth; 1.
DR PRINTS; PR00151; PORPHBDMNASE.
DR SUPFAM; SSF54782; SSF54782; 1.
DR TIGRFAMs; TIGR00212; hemC; 1.
DR PROSITE; PS00533; PORPHOBILINOGEN_DEAM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Porphyrin biosynthesis;
KW Reference proteome; Transferase.
FT CHAIN 1..313
FT /note="Porphobilinogen deaminase"
FT /id="PRO_0000142934"
FT MOD_RES 242
FT /note="S-(dipyrrolylmethanemethyl)cysteine"
FT MUTAGEN 7
FT /note="R->L: No loss of activity."
FT MUTAGEN 11
FT /note="R->L: Loss of activity."
FT MUTAGEN 55
FT /note="K->Q: No loss of activity."
FT /evidence="ECO:0000269|PubMed:2122889"
FT MUTAGEN 59
FT /note="K->Q: 25-fold decrease in activity."
FT /evidence="ECO:0000269|PubMed:2122889"
FT MUTAGEN 101
FT /note="R->L: No loss of activity."
FT MUTAGEN 131
FT /note="R->L: Complete loss of activity."
FT MUTAGEN 132
FT /note="R->L: Complete loss of activity."
FT MUTAGEN 155
FT /note="R->L: Loss of activity."
FT MUTAGEN 176
FT /note="R->L: Loss of activity."
FT CONFLICT 137
FT /note="A -> G (in Ref. 3; AAA67601)"
FT /evidence="ECO:0000305"
FT CONFLICT 186
FT /note="A -> G (in Ref. 3; AAA67601)"
FT /evidence="ECO:0000305"
FT CONFLICT 241
FT /note="G -> A (in Ref. 1; CAA27813)"
FT /evidence="ECO:0000305"
FT CONFLICT 261
FT /note="A -> G (in Ref. 1; CAA27813)"
FT /evidence="ECO:0000305"
FT CONFLICT 265
FT /note="A -> R (in Ref. 3; AAA67601)"
FT /evidence="ECO:0000305"
FT STRAND 5..10
FT /evidence="ECO:0007829|PDB:1GTK"
FT HELIX 14..30
FT /evidence="ECO:0007829|PDB:1GTK"
FT STRAND 35..40
FT /evidence="ECO:0007829|PDB:1GTK"
FT HELIX 44..47
FT /evidence="ECO:0007829|PDB:1PDA"
FT HELIX 63..71
FT /evidence="ECO:0007829|PDB:1GTK"
FT STRAND 76..81
FT /evidence="ECO:0007829|PDB:1GTK"
FT HELIX 82..84
FT /evidence="ECO:0007829|PDB:1GTK"
FT STRAND 93..98
FT /evidence="ECO:0007829|PDB:1GTK"
FT STRAND 106..109
FT /evidence="ECO:0007829|PDB:1GTK"
FT HELIX 116..118
FT /evidence="ECO:0007829|PDB:1GTK"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:1GTK"
FT HELIX 130..139
FT /evidence="ECO:0007829|PDB:1GTK"
FT STRAND 143..146
FT /evidence="ECO:0007829|PDB:1GTK"
FT HELIX 152..160
FT /evidence="ECO:0007829|PDB:1GTK"
FT STRAND 165..170
FT /evidence="ECO:0007829|PDB:1GTK"
FT HELIX 171..176
FT /evidence="ECO:0007829|PDB:1GTK"
FT HELIX 180..182
FT /evidence="ECO:0007829|PDB:1GTK"
FT STRAND 184..186
FT /evidence="ECO:0007829|PDB:1GTK"
FT TURN 189..191
FT /evidence="ECO:0007829|PDB:1GTK"
FT TURN 196..199
FT /evidence="ECO:0007829|PDB:1GTK"
FT STRAND 201..206
FT /evidence="ECO:0007829|PDB:1GTK"
FT HELIX 210..216
FT /evidence="ECO:0007829|PDB:1GTK"
FT HELIX 217..219
FT /evidence="ECO:0007829|PDB:1GTK"
FT HELIX 222..238
FT /evidence="ECO:0007829|PDB:1GTK"
FT STRAND 242..244
FT /evidence="ECO:0007829|PDB:2YPN"
FT STRAND 246..253
FT /evidence="ECO:0007829|PDB:1GTK"
FT STRAND 256..264
FT /evidence="ECO:0007829|PDB:1GTK"
FT STRAND 271..278
FT /evidence="ECO:0007829|PDB:1GTK"
FT HELIX 280..282
FT /evidence="ECO:0007829|PDB:1GTK"
FT HELIX 283..296
FT /evidence="ECO:0007829|PDB:1GTK"
FT HELIX 299..304
FT /evidence="ECO:0007829|PDB:1GTK"
FT TURN 305..308
FT /evidence="ECO:0007829|PDB:1GTK"
SQ SEQUENCE 313 AA; 33852 MW; 7276981B52C7D1E3 CRC64;
MLDNVLRIAT RQSPLALWQA HYVKDKLMAS HPGLVVELVP MVTRGDVILD TPLAKVGGKG
LFVKELEVAL LENRADIAVH SMKDVPVEFP QGLGLVTICE REDPRDAFVS NNYDSLDALP
AGSIVGTSSL RRQCQLAERR PDLIIRSLRG NVGTRLSKLD NGEYDAIILA VAGLKRLGLE
SRIRAALPPE ISLPAVGQGA VGIECRLDDS RTRELLAALN HHETALRVTA ERAMNTRLEG
GCQVPIGSYA ELIDGEIWLR ALVGAPDGSQ IIRGERRGAP QDAEQMGISL AEELLNNGAR
EILAEVYNGD APA
