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 27-MAR-2024, entry version 209. 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; Pseudomonadota; 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 511145-b3805; -. DR EnsemblBacteria; AAT48218; AAT48218; b3805. 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 OrthoDB; 9810298at2; -. DR PhylomeDB; P06983; -. DR BioCyc; EcoCyc:OHMETHYLBILANESYN-MONOMER; -. DR BioCyc; MetaCyc:OHMETHYLBILANESYN-MONOMER; -. DR BRENDA; 2.5.1.61; 2026. DR SABIO-RK; P06983; -. 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:0006782; P:protoporphyrinogen IX biosynthetic process; IDA:EcoCyc. DR GO; GO:0033014; P:tetrapyrrole biosynthetic process; IMP:EcoliWiki. DR CDD; cd13646; PBP2_EcHMBS_like; 1. DR Gene3D; 3.40.190.10; Periplasmic binding protein-like II; 2. DR Gene3D; 3.30.160.40; Porphobilinogen deaminase, C-terminal domain; 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 NCBIfam; TIGR00212; hemC; 1. DR PANTHER; PTHR11557; PORPHOBILINOGEN DEAMINASE; 1. DR PANTHER; PTHR11557:SF0; PORPHOBILINOGEN DEAMINASE; 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; SSF53850; Periplasmic binding protein-like II; 1. DR SUPFAM; SSF54782; Porphobilinogen deaminase (hydroxymethylbilane synthase), C-terminal domain; 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 //