HEM2_PSEAE
ID HEM2_PSEAE Reviewed; 337 AA.
AC Q59643;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Delta-aminolevulinic acid dehydratase;
DE Short=ALAD;
DE Short=ALADH;
DE EC=4.2.1.24;
DE AltName: Full=Porphobilinogen synthase;
GN Name=hemB; OrderedLocusNames=PA5243;
OS Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM
OS 14847 / LMG 12228 / 1C / PRS 101 / PAO1).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pseudomonadales;
OC Pseudomonadaceae; Pseudomonas.
OX NCBI_TaxID=208964;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=9529530; DOI=10.1007/s004380050673;
RA Frankenberg N., Kittel T., Hungerer C., Roemling U., Jahn D.;
RT "Cloning, mapping and functional characterization of the hemB gene of
RT Pseudomonas aeruginosa, which encodes a magnesium-dependent 5-
RT aminolevulinic acid dehydratase.";
RL Mol. Gen. Genet. 257:485-489(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=10984043; DOI=10.1038/35023079;
RA Stover C.K., Pham X.-Q.T., Erwin A.L., Mizoguchi S.D., Warrener P.,
RA Hickey M.J., Brinkman F.S.L., Hufnagle W.O., Kowalik D.J., Lagrou M.,
RA Garber R.L., Goltry L., Tolentino E., Westbrock-Wadman S., Yuan Y.,
RA Brody L.L., Coulter S.N., Folger K.R., Kas A., Larbig K., Lim R.M.,
RA Smith K.A., Spencer D.H., Wong G.K.-S., Wu Z., Paulsen I.T., Reizer J.,
RA Saier M.H. Jr., Hancock R.E.W., Lory S., Olson M.V.;
RT "Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic
RT pathogen.";
RL Nature 406:959-964(2000).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.67 ANGSTROMS) IN COMPLEX WITH LEVULINIC ACID AND
RP MAGNESIUM, AND SUBUNIT.
RX PubMed=10356331; DOI=10.1006/jmbi.1999.2808;
RA Frankenberg N., Erskine P.T., Cooper J.B., Shoolingin-Jordan P.M., Jahn D.,
RA Heinz D.W.;
RT "High resolution crystal structure of a Mg(2+)-dependent porphobilinogen
RT synthase.";
RL J. Mol. Biol. 289:591-602(1999).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.66 ANGSTROMS) OF MUTANT ASN-139 IN COMPLEX WITH
RP 5-FLUOROLEVULINIC ACID AND MAGNESIUM, COFACTOR, AND ACTIVE SITE.
RX PubMed=12079382; DOI=10.1016/s0022-2836(02)00472-2;
RA Frere F., Schubert W.-D., Stauffer F., Frankenberg N., Neier R., Jahn D.,
RA Heinz D.W.;
RT "Structure of porphobilinogen synthase from Pseudomonas aeruginosa in
RT complex with 5-fluorolevulinic acid suggests a double Schiff base
RT mechanism.";
RL J. Mol. Biol. 320:237-247(2002).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.48 ANGSTROMS) IN COMPLEXES WITH MAGNESIUM;
RP 5-HYDROXYLEVULINIC ACID AND OTHER INHIBITORS, CATALYTIC ACTIVITY, COFACTOR,
RP AND ACTIVE SITE.
RX PubMed=16819823; DOI=10.1021/bi052611f;
RA Frere F., Nentwich M., Gacond S., Heinz D.W., Neier R.,
RA Frankenberg-Dinkel N.;
RT "Probing the active site of Pseudomonas aeruginosa porphobilinogen synthase
RT using newly developed inhibitors.";
RL Biochemistry 45:8243-8253(2006).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEX WITH ALAREMYCIN.
RX PubMed=19822707; DOI=10.1128/aac.00553-09;
RA Heinemann I.U., Schulz C., Schubert W.D., Heinz D.W., Wang Y.G.,
RA Kobayashi Y., Awa Y., Wachi M., Jahn D., Jahn M.;
RT "Structure of the heme biosynthetic Pseudomonas aeruginosa porphobilinogen
RT synthase in complex with the antibiotic alaremycin.";
RL Antimicrob. Agents Chemother. 54:267-272(2010).
CC -!- FUNCTION: Catalyzes an early step in the biosynthesis of tetrapyrroles.
CC Binds two molecules of 5-aminolevulinate per subunit, each at a
CC distinct site, and catalyzes their condensation to form porphobilinogen
CC (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 5-aminolevulinate = H(+) + 2 H2O + porphobilinogen;
CC Xref=Rhea:RHEA:24064, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:58126, ChEBI:CHEBI:356416; EC=4.2.1.24;
CC Evidence={ECO:0000269|PubMed:16819823};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:12079382, ECO:0000269|PubMed:16819823};
CC -!- ACTIVITY REGULATION: Stimulated by magnesium ions.
CC -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX
CC biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 1/4.
CC -!- SUBUNIT: Homooctamer; formed by oligomerization of dimers.
CC {ECO:0000269|PubMed:10356331, ECO:0000269|PubMed:12079382,
CC ECO:0000269|PubMed:19822707}.
CC -!- SIMILARITY: Belongs to the ALAD family. {ECO:0000305}.
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DR EMBL; X91820; CAA62930.1; -; Genomic_DNA.
DR EMBL; AE004091; AAG08628.1; -; Genomic_DNA.
DR PIR; S60577; S60577.
DR RefSeq; NP_253930.1; NC_002516.2.
DR RefSeq; WP_003096352.1; NZ_QZGE01000002.1.
DR PDB; 1B4K; X-ray; 1.67 A; A/B=1-337.
DR PDB; 1GZG; X-ray; 1.66 A; A/B=1-337.
DR PDB; 1W54; X-ray; 2.20 A; A/B=1-337.
DR PDB; 1W56; X-ray; 1.70 A; A/B=1-337.
DR PDB; 1W5M; X-ray; 1.60 A; A/B=1-337.
DR PDB; 1W5N; X-ray; 1.65 A; A/B=1-337.
DR PDB; 1W5O; X-ray; 1.85 A; A/B=1-337.
DR PDB; 1W5P; X-ray; 1.55 A; A/B=1-337.
DR PDB; 1W5Q; X-ray; 1.40 A; A/B=1-337.
DR PDB; 2C13; X-ray; 2.15 A; A/B=1-337.
DR PDB; 2C14; X-ray; 1.90 A; A/B=1-337.
DR PDB; 2C15; X-ray; 1.48 A; A/B=1-337.
DR PDB; 2C16; X-ray; 2.02 A; A/B=1-337.
DR PDB; 2C18; X-ray; 1.93 A; A/B=1-337.
DR PDB; 2C19; X-ray; 2.05 A; A/B=1-337.
DR PDB; 2WOQ; X-ray; 1.75 A; A=1-337.
DR PDBsum; 1B4K; -.
DR PDBsum; 1GZG; -.
DR PDBsum; 1W54; -.
DR PDBsum; 1W56; -.
DR PDBsum; 1W5M; -.
DR PDBsum; 1W5N; -.
DR PDBsum; 1W5O; -.
DR PDBsum; 1W5P; -.
DR PDBsum; 1W5Q; -.
DR PDBsum; 2C13; -.
DR PDBsum; 2C14; -.
DR PDBsum; 2C15; -.
DR PDBsum; 2C16; -.
DR PDBsum; 2C18; -.
DR PDBsum; 2C19; -.
DR PDBsum; 2WOQ; -.
DR AlphaFoldDB; Q59643; -.
DR SMR; Q59643; -.
DR STRING; 287.DR97_2613; -.
DR BindingDB; Q59643; -.
DR ChEMBL; CHEMBL3286086; -.
DR DrugBank; DB02828; 5-Fluorolevulinic Acid.
DR DrugBank; DB01942; Formic acid.
DR PaxDb; Q59643; -.
DR PRIDE; Q59643; -.
DR DNASU; 879701; -.
DR EnsemblBacteria; AAG08628; AAG08628; PA5243.
DR GeneID; 879701; -.
DR KEGG; pae:PA5243; -.
DR PATRIC; fig|208964.12.peg.5495; -.
DR PseudoCAP; PA5243; -.
DR HOGENOM; CLU_035731_0_0_6; -.
DR InParanoid; Q59643; -.
DR OMA; YQMDYAN; -.
DR PhylomeDB; Q59643; -.
DR BioCyc; PAER208964:G1FZ6-5363-MON; -.
DR BRENDA; 4.2.1.24; 5087.
DR UniPathway; UPA00251; UER00318.
DR EvolutionaryTrace; Q59643; -.
DR PRO; PR:Q59643; -.
DR Proteomes; UP000002438; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0004655; F:porphobilinogen synthase activity; IMP:PseudoCAP.
DR GO; GO:0008270; F:zinc ion binding; IBA:GO_Central.
DR GO; GO:0006783; P:heme biosynthetic process; IBA:GO_Central.
DR GO; GO:0006779; P:porphyrin-containing compound biosynthetic process; IMP:PseudoCAP.
DR GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR001731; ALAD.
DR InterPro; IPR030656; ALAD_AS.
DR InterPro; IPR013785; Aldolase_TIM.
DR PANTHER; PTHR11458; PTHR11458; 1.
DR Pfam; PF00490; ALAD; 1.
DR PIRSF; PIRSF001415; Porphbilin_synth; 1.
DR PRINTS; PR00144; DALDHYDRTASE.
DR SMART; SM01004; ALAD; 1.
DR PROSITE; PS00169; D_ALA_DEHYDRATASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Heme biosynthesis; Lyase; Magnesium; Metal-binding;
KW Porphyrin biosynthesis; Reference proteome.
FT CHAIN 1..337
FT /note="Delta-aminolevulinic acid dehydratase"
FT /id="PRO_0000140507"
FT ACT_SITE 205
FT /note="Schiff-base intermediate with substrate"
FT /evidence="ECO:0000269|PubMed:12079382,
FT ECO:0000269|PubMed:16819823"
FT ACT_SITE 260
FT /note="Schiff-base intermediate with substrate"
FT /evidence="ECO:0000269|PubMed:12079382,
FT ECO:0000269|PubMed:16819823"
FT BINDING 215
FT /ligand="5-aminolevulinate"
FT /ligand_id="ChEBI:CHEBI:356416"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10356331,
FT ECO:0000269|PubMed:12079382"
FT BINDING 229
FT /ligand="5-aminolevulinate"
FT /ligand_id="ChEBI:CHEBI:356416"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10356331,
FT ECO:0000269|PubMed:12079382"
FT BINDING 245
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:10356331,
FT ECO:0000269|PubMed:12079382"
FT BINDING 286
FT /ligand="5-aminolevulinate"
FT /ligand_id="ChEBI:CHEBI:356416"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10356331,
FT ECO:0000269|PubMed:12079382"
FT BINDING 324
FT /ligand="5-aminolevulinate"
FT /ligand_id="ChEBI:CHEBI:356416"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10356331,
FT ECO:0000269|PubMed:12079382"
FT TURN 10..12
FT /evidence="ECO:0007829|PDB:1W5Q"
FT TURN 15..19
FT /evidence="ECO:0007829|PDB:1W5Q"
FT HELIX 22..28
FT /evidence="ECO:0007829|PDB:1W5Q"
FT HELIX 35..37
FT /evidence="ECO:0007829|PDB:1W5Q"
FT STRAND 38..49
FT /evidence="ECO:0007829|PDB:1W5Q"
FT STRAND 51..53
FT /evidence="ECO:0007829|PDB:1W5Q"
FT STRAND 61..64
FT /evidence="ECO:0007829|PDB:1W5Q"
FT HELIX 65..77
FT /evidence="ECO:0007829|PDB:1W5Q"
FT STRAND 82..87
FT /evidence="ECO:0007829|PDB:1W5Q"
FT HELIX 91..93
FT /evidence="ECO:0007829|PDB:1W5Q"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:1W5Q"
FT HELIX 99..102
FT /evidence="ECO:0007829|PDB:1W5Q"
FT HELIX 107..118
FT /evidence="ECO:0007829|PDB:1W5Q"
FT STRAND 122..128
FT /evidence="ECO:0007829|PDB:1W5Q"
FT TURN 131..133
FT /evidence="ECO:0007829|PDB:1W5Q"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:1W5P"
FT HELIX 150..166
FT /evidence="ECO:0007829|PDB:1W5Q"
FT STRAND 170..174
FT /evidence="ECO:0007829|PDB:1W5Q"
FT HELIX 181..191
FT /evidence="ECO:0007829|PDB:1W5Q"
FT STRAND 198..206
FT /evidence="ECO:0007829|PDB:1W5Q"
FT HELIX 209..211
FT /evidence="ECO:0007829|PDB:1W5Q"
FT HELIX 212..216
FT /evidence="ECO:0007829|PDB:1W5Q"
FT HELIX 221..224
FT /evidence="ECO:0007829|PDB:2C15"
FT HELIX 229..231
FT /evidence="ECO:0007829|PDB:1W5Q"
FT STRAND 232..234
FT /evidence="ECO:0007829|PDB:1W54"
FT HELIX 240..251
FT /evidence="ECO:0007829|PDB:1W5Q"
FT STRAND 255..261
FT /evidence="ECO:0007829|PDB:1W5Q"
FT HELIX 263..265
FT /evidence="ECO:0007829|PDB:1W5Q"
FT HELIX 266..276
FT /evidence="ECO:0007829|PDB:1W5Q"
FT STRAND 280..284
FT /evidence="ECO:0007829|PDB:1W5Q"
FT HELIX 286..297
FT /evidence="ECO:0007829|PDB:1W5Q"
FT HELIX 305..316
FT /evidence="ECO:0007829|PDB:1W5Q"
FT STRAND 319..323
FT /evidence="ECO:0007829|PDB:1W5Q"
FT HELIX 326..334
FT /evidence="ECO:0007829|PDB:1W5Q"
SQ SEQUENCE 337 AA; 37037 MW; 7D650C49795D542C CRC64;
MSFTPANRAY PYTRLRRNRR DDFSRRLVRE NVLTVDDLIL PVFVLDGVNQ RESIPSMPGV
ERLSIDQLLI EAEEWVALGI PALALFPVTP VEKKSLDAAE AYNPEGIAQR ATRALRERFP
ELGIITDVAL DPFTTHGQDG ILDDDGYVLN DVSIDVLVRQ ALSHAEAGAQ VVAPSDMMDG
RIGAIREALE SAGHTNVRIM AYSAKYASAY YGPFRDAVGS ASNLGKGNKA TYQMDPANSD
EALHEVAADL AEGADMVMVK PGMPYLDIVR RVKDEFRAPT FVYQVSGEYA MHMGAIQNGW
LAESVILESL TAFKRAGADG ILTYFAKQAA EQLRRGR
