DB code: S00537

RLCP classification 6.10.398000.111 : Double-bonded atom exchange
6.10.431300.120 : Double-bonded atom exchange
8.11121.166400.120 : Isomerization
CATH domain 3.20.20.70 : TIM Barrel Catalytic domain
E.C. 4.2.1.24
CSA
M-CSA
MACiE M0230

CATH domain Related DB codes (homologues)
3.20.20.70 : TIM Barrel S00215 S00217 S00218 S00219 S00532 S00198 S00220 S00745 S00538 S00539 S00826 S00841 S00235 S00239 S00240 S00243 S00244 S00199 S00200 S00201 S00221 S00222 S00847 S00224 S00225 S00226 D00014 D00029 M00141 T00015 T00239 D00664 D00665 D00804 D00863 T00089

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q59643 Delta-aminolevulinic acid dehydratase
ALADH
ALAD
EC 4.2.1.24
Porphobilinogen synthase
NP_253930.1 (Protein)
NC_002516.2 (DNA/RNA sequence)
PF00490 (ALAD)
[Graphical View]

KEGG enzyme name
porphobilinogen synthase
aminolevulinate dehydratase
delta-aminolevulinate dehydratase
delta-aminolevulinic acid dehydrase
delta-aminolevulinic acid dehydratase
aminolevulinic dehydratase
delta-aminolevulinic dehydratase
5-levulinic acid dehydratase
5-aminolevulinate hydro-lyase (adding 5-aminolevulinate andcyclizing)

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q59643 HEM2_PSEAE 2 5-aminolevulinate = porphobilinogen + 2 H(2)O. Homooctamer (By similarity). Magnesium.

KEGG Pathways
Map code Pathways E.C.
MAP00860 Porphyrin and chlorophyll metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C01330 C00430 C00931 C00001
E.C.
Compound Magnesium Sodium 5-Aminolevulinate Porphobilinogen H2O P-side ALA carbinolamine transition-state P-side ALA Schiff-base intermediate A-side ALA carbinolamine + P-side ALA Schiff-base intermediate A-side/P-side ALA Schiff-base intermediate A-side enamine + P-side Schiff-base intermediate C-C bonded intermediate C-N bonded intermediate
Type divalent metal (Ca2+, Mg2+) univalent metal (Na+, K+) amino acids,carbohydrate amine group,aromatic ring (with nitrogen atoms),carboxyl group H2O
ChEBI 18420
 18420
 		29101
 29101
 		17549
 356416
 17549
 356416
 		17381
 17381
 		15377
 15377
PubChem 888
 888
 		923
 923
 		137
 7048523
 137
 7048523
 		1021
 1021
 		22247451
 962
 22247451
 962
1b4kA Bound:_MG Unbound Unbound Unbound Unbound Intermediate-analogue:LEA Unbound Unbound Unbound Unbound Unbound
1b4kB Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:LEA Unbound Unbound Unbound Unbound Unbound
1gzgA Bound:_MG Bound:_NA Unbound Unbound Unbound Intermediate-analogue:LAF_1337 Unbound Intermediate-analogue:LAF_1336 Unbound Unbound Unbound
1gzgB Bound:_MG Bound:_NA Analogue:LAF_1338 (A-side) Unbound Unbound Intermediate-analogue:LAF_1337 Unbound Intermediate-analogue:LAF_1336 Unbound Unbound Unbound
1w54A Bound:_MG Analogue:_ZN Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w54B Bound:_MG Analogue:_ZN Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w56A Bound:_MG Analogue:_ZN Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w56B Bound:_MG Analogue:_ZN Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w5mA Bound:_MG Analogue:_ZN Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w5mB Bound:_MG Analogue:_ZN Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w5nA Bound:_MG Analogue:_ZN Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w5nB Bound:_MG Analogue:_ZN Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w5oA Bound:_MG Analogue:_ZN Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w5oB Bound:_MG Analogue:_ZN Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w5pA Bound:_MG Analogue:_ZN Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w5pB Bound:_MG Analogue:_ZN Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w5qA Bound:_MG Analogue:_ZN Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1w5qB Bound:_MG Analogue:_ZN Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
2c13A Bound:_MG Unbound Unbound Unbound Unbound Intermediate-analogue:FHL_260 Unbound Intermediate-analogue:FHL_205 Unbound Unbound Unbound
2c13B Bound:_MG Unbound Unbound Unbound Unbound Intermediate-analogue:FHL_260 Unbound Intermediate-analogue:FHL_205 Unbound Unbound Unbound
2c14A Bound:_MG Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:CYJ_205
2c14B Bound:_MG Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:CYJ_205
2c15A Bound:_MG Unbound Analogue:LET_260 (A-side) Unbound Unbound Intermediate-analogue:LET_260 Unbound Unbound Unbound Unbound Unbound
2c15B Bound:_MG Unbound Analogue:LET_260 (A-side) Unbound Unbound Intermediate-analogue:LET_260 Unbound Unbound Unbound Unbound Unbound
2c16A Bound:_MG Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:OBS_205
2c16B Bound:_MG Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:OBS_205
2c18A Bound:_MG_1337 Analogue:_MG_1338 Analogue:LSO_260 (A-side) Unbound Unbound Intermediate-analogue:LSO_260 Unbound Unbound Unbound Unbound Unbound
2c18B Bound:_MG_1337 Analogue:_MG_1338 Analogue:LSO_260 (A-side) Unbound Unbound Intermediate-analogue:LSO_260 Unbound Unbound Unbound Unbound Unbound
2c19A Bound:_MG Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:C1X_205
2c19B Bound:_MG Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Intermediate-analogue:C1X_205

Reference for Active-site residues
resource references E.C.

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1b4kA LYS 205;LYS 260 ASP 127;ASP 131;SER 175(Sodium binding);GLU 245(Magnesium binding)
1b4kB LYS 205;LYS 260 ASP 127;ASP 131;SER 175(Sodium binding);GLU 245(Magnesium binding)
1gzgA LYS 205;LYS 260 ASP 127;ASP 131;SER 175(Sodium binding);GLU 245(Magnesium binding) mutant D139N
1gzgB LYS 205;LYS 260 ASP 127;ASP 131;SER 175(Sodium binding);GLU 245(Magnesium binding) mutant D139N
1w54A LYS 205;LYS 260 ASP 127;ASP 131;SER 175(Sodium binding);GLU 245(Magnesium binding) mutant D139C
1w54B LYS 205;LYS 260 ASP 127;ASP 131;SER 175(Sodium binding);GLU 245(Magnesium binding) mutant D139C
1w56A LYS 205;LYS 260 ASP 127;;SER 175(Sodium binding);GLU 245(Magnesium binding) mutant A129C, D131C
1w56B LYS 205;LYS 260 ASP 127;;SER 175(Sodium binding);GLU 245(Magnesium binding) mutant A129C, D131C
1w5mA LYS 205;LYS 260 ASP 127;ASP 131;SER 175(Sodium binding);GLU 245(Magnesium binding) mutant A129C, D139C
1w5mB LYS 205;LYS 260 ASP 127;ASP 131;SER 175(Sodium binding);GLU 245(Magnesium binding) mutant A129C, D139C
1w5nA LYS 205;LYS 260 ASP 127;;SER 175(Sodium binding);GLU 245(Magnesium binding) mutant D131C, D139C
1w5nB LYS 205;LYS 260 ASP 127;;SER 175(Sodium binding);GLU 245(Magnesium binding) mutant D131C, D139C
1w5oA LYS 205;LYS 260 ASP 127;;SER 175(Sodium binding);GLU 245(Magnesium binding) mutant A129C, D131C, D139C
1w5oB LYS 205;LYS 260 ASP 127;;SER 175(Sodium binding);GLU 245(Magnesium binding) mutant A129C, D131C, D139C
1w5pA LYS 205;LYS 260 ASP 127;;SER 175(Sodium binding);GLU 245(Magnesium binding) mutant A129C, D131C, D139C, P132E
1w5pB LYS 205;LYS 260 ASP 127;;SER 175(Sodium binding);GLU 245(Magnesium binding) mutant A129C, D131C, D139C, P132E
1w5qA LYS 205;LYS 260 ASP 127;;SER 175(Sodium binding);GLU 245(Magnesium binding) mutant A129C, D131C, D139C, P132E, K229R
1w5qB LYS 205;LYS 260 ASP 127;;SER 175(Sodium binding);GLU 245(Magnesium binding) mutant A129C, D131C, D139C, P132E, K229R
2c13A ; ASP 127;ASP 131;SER 175(Sodium binding);GLU 245(Magnesium binding) FHL 205;FHL 260
2c13B ; ASP 127;ASP 131;SER 175(Sodium binding);GLU 245(Magnesium binding) FHL 205;FHL 260
2c14A ;LYS 260 ASP 127;ASP 131;SER 175(Sodium binding);GLU 245(Magnesium binding) CYJ 205;
2c14B ;LYS 260 ASP 127;ASP 131;SER 175(Sodium binding);GLU 245(Magnesium binding) CYJ 205;
2c15A LYS 205; ASP 127;ASP 131;SER 175(Sodium binding);GLU 245(Magnesium binding) ;LET 260
2c15B LYS 205; ASP 127;ASP 131;SER 175(Sodium binding);GLU 245(Magnesium binding) ;LET 260
2c16A ;LYS 260 ASP 127;ASP 131;SER 175(Sodium binding);GLU 245(Magnesium binding) OBS 205;
2c16B ;LYS 260 ASP 127;ASP 131;SER 175(Sodium binding);GLU 245(Magnesium binding) OBS 205;
2c18A LYS 205; ASP 127;ASP 131;SER 175(Sodium binding);GLU 245(Magnesium binding) ;LSO 260
2c18B LYS 205; ASP 127;ASP 131;SER 175(Sodium binding);GLU 245(Magnesium binding) ;LSO 260
2c19A ;LYS 260 ASP 127;ASP 131;SER 175(Sodium binding);GLU 245(Magnesium binding) C1X 205;
2c19B ;LYS 260 ASP 127;ASP 131;SER 175(Sodium binding);GLU 245(Magnesium binding) C1X 205;

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
Scheme 2, p.285 5
[5]
Fig.1, p.8346
[7]
Fig.7, p.2122
[11]
Fig.1, Fig.2, p.11561
[13]
Fig.3, p.169-175 2
[17]
p.1027
[20]
Fig.7, p.4273-4275
[23]
Fig.1, p.599
[24]
Fig.6, p.1254
[25]
p.428
[27]
Fig.8, p.191-194 11
[28]
p.8234-8256
[29]
Fig.4, p.199-200 8
[31]
p.138-139
[33]
Scheme 2, p.589-590 7
[34]
p.19797-19798
[35]
Fig.6, p.243-245 10
[36]
Scheme 2, p.736-737 8
[38]
p.567-568
[41]
p.1225-1226
[42]
Fig.5, p.8251-8252

References
[1]
Resource
Comments
Medline ID
PubMed ID 6967019
Journal FEBS Lett
Year 1980
Volume 114
Pages 283-6
Authors Jordan PM, Seehra JS
Title 13C NMR as a probe for the study of enzyme-catalysed reactions: mechanism of action of 5-aminolevulinic acid dehydratase.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 3663587
Journal Biochemistry
Year 1987
Volume 26
Pages 4258-64
Authors Jaffe EK, Markham GD
Title 13C NMR studies of porphobilinogen synthase: observation of intermediates bound to a 280,000-dalton protein.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 3166990
Journal Biochemistry
Year 1988
Volume 27
Pages 4475-81
Authors Jaffe EK, Markham GD
Title 13C NMR studies of methylene and methine carbons of substrate bound to a 280,000-dalton protein, porphobilinogen synthase.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 3242540
Journal Biol Chem Hoppe Seyler
Year 1988
Volume 369
Pages 1099-103
Authors Pilz I, Schwarz E, Vuga M, Beyersmann D
Title Small angle X-ray scattering study on bovine porphobilinogen synthase (5-aminolaevulinate dehydratase).
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 2252894
Journal Biochemistry
Year 1990
Volume 29
Pages 8345-50
Authors Jaffe EK, Markham GD, Rajagopalan JS
Title 15N and 13C NMR studies of ligands bound to the 280,000-dalton protein porphobilinogen synthase elucidate the structures of enzyme-bound product and a Schiff base intermediate.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 1965291
Journal Biol Chem Hoppe Seyler
Year 1990
Volume 371
Pages 1145-52
Authors Block C, Lohmann RD, Beyersmann D
Title Probing of active site residues of the zinc enzyme 5-aminolevulinate dehydratase by spin and fluorescence labels.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 1346974
Journal Biochemistry
Year 1992
Volume 31
Pages 2113-23
Authors Jaffe EK, Abrams WR, Kaempfen HX, Harris KA Jr
Title 5-Chlorolevulinate modification of porphobilinogen synthase identifies a potential role for the catalytic zinc.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 8424649
Journal Arch Biochem Biophys
Year 1993
Volume 300
Pages 169-77
Authors Mitchell LW, Jaffe EK
Title Porphobilinogen synthase from Escherichia coli is a Zn(II) metalloenzyme stimulated by Mg(II).
Related PDB
Related UniProtKB
[9]
Resource
Comments CHARACTERIZATION, AND SEQUENCE OF 1-5; 95-134 AND 237-253.
Medline ID 93176130
PubMed ID 8439296
Journal Biochem J
Year 1993
Volume 290
Pages 279-87
Authors Spencer P, Jordan PM
Title Purification and characterization of 5-aminolaevulinic acid dehydratase from Escherichia coli and a study of the reactive thiols at the metal-binding domain.
Related PDB
Related UniProtKB P15002
[10]
Resource
Comments
Medline ID
PubMed ID 8382991
Journal Protein Sci
Year 1993
Volume 2
Pages 71-9
Authors Markham GD, Myers CB, Harris KA Jr, Volin M, Jaffe EK
Title Spatial proximity and sequence localization of the reactive sulfhydryls of porphobilinogen synthase.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 7918369
Journal Biochemistry
Year 1994
Volume 33
Pages 11554-62
Authors Jaffe EK, Volin M, Myers CB, Abrams WR
Title 5-Chloro[1,4-13C]levulinic acid modification of mammalian and bacterial porphobilinogen synthase suggests an active site containing two Zn(II).
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 7819203
Journal Biochemistry
Year 1995
Volume 34
Pages 244-51
Authors Jaffe EK, Ali S, Mitchell LW, Taylor KM, Volin M, Markham GD
Title Characterization of the role of the stimulatory magnesium of Escherichia coli porphobilinogen synthase.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 7592564
Journal J Bioenerg Biomembr
Year 1995
Volume 27
Pages 169-79
Authors Jaffe EK
Title Porphobilinogen synthase, the first source of heme's asymmetry.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 7592604
Journal J Biol Chem
Year 1995
Volume 270
Pages 24054-9
Authors Mitchell LW, Volin M, Jaffe EK
Title The phylogenetically conserved histidines of Escherichia coli porphobilinogen synthase are not required for catalysis.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 8612634
Journal Eur J Biochem
Year 1996
Volume 236
Pages 600-8
Authors Stolz M, Dornemann D
Title Purification, metal cofactor, N-terminal sequence and subunit composition of a 5-aminolevulinic acid dehydratase from the unicellular green alga Scenedesmus obliquus, mutant C-2A'.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 9341235
Journal Biochemistry
Year 1997
Volume 36
Pages 13421-7
Authors Petrovich RM, Jaffe EK
Title Magnetic resonance studies on the active site and metal centers of Bradyrhizobium japonicum porphobilinogen synthase.
Related PDB
Related UniProtKB
[17]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
Medline ID 98069651
PubMed ID 9406553
Journal Nat Struct Biol
Year 1997
Volume 4
Pages 1025-31
Authors Erskine PT, Senior N, Awan S, Lambert R, Lewis G, Tickle IJ, Sarwar M, Spencer P, Thomas P, Warren MJ, Shoolingin-Jordan PM, Wood SP, Cooper JB
Title X-ray structure of 5-aminolaevulinate dehydratase, a hybrid aldolase.
Related PDB 1aw5
Related UniProtKB P05373
[18]
Resource
Comments
Medline ID
PubMed ID 9260292
Journal Protein Sci
Year 1997
Volume 6
Pages 1774-6
Authors Erskine PT, Senior N, Maignan S, Cooper J, Lambert R, Lewis G, Spencer P, Awan S, Warren M, Tickle IJ, Thomas P, Wood SP, Shoolingin-Jordan PM
Title Crystallization of 5-aminolaevulinic acid dehydratase from Escherichia coli and Saccharomyces cerevisiae and preliminary X-ray characterization of the crystals.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 9766004
Journal Biochem Soc Trans
Year 1998
Volume 26
Pages S285
Authors Norton E, Sarwar M, Shoolingin-Jordan P
Title Mechanistic studies on E.coli 5-aminolaevulinic acid dehydratase.
Related PDB
Related UniProtKB
[20]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
Medline ID 99211872
PubMed ID 10194344
Journal Biochemistry
Year 1999
Volume 38
Pages 4266-76
Authors Erskine PT, Norton E, Cooper JB, Lambert R, Coker A, Lewis G, Spencer P, Sarwar M, Wood SP, Warren MJ, Shoolingin-Jordan PM
Title X-ray structure of 5-aminolevulinic acid dehydratase from Escherichia coli complexed with the inhibitor levulinic acid at 2.0 A resolution.
Related PDB 1b4e
Related UniProtKB P15002
[21]
Resource
Comments
Medline ID
PubMed ID 10529243
Journal Biochemistry
Year 1999
Volume 38
Pages 13968-75
Authors Frankenberg N, Heinz DW, Jahn D
Title Production, purification, and characterization of a Mg2+-responsive porphobilinogen synthase from Pseudomonas aeruginosa.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 10529244
Journal Biochemistry
Year 1999
Volume 38
Pages 13976-82
Authors Frankenberg N, Jahn D, Jaffe EK
Title Pseudomonas aeruginosa contains a novel type V porphobilinogen synthase with no required catalytic metal ions.
Related PDB
Related UniProtKB
[23]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.67 ANGSTROMS).
Medline ID 99286289
PubMed ID 10356331
Journal J Mol Biol
Year 1999
Volume 289
Pages 591-602
Authors Frankenberg N, Erskine PT, Cooper JB, Shoolingin-Jordan PM, Jahn D, Heinz DW
Title High resolution crystal structure of a Mg2+-dependent porphobilinogen synthase.
Related PDB 1b4k
Related UniProtKB Q59643
[24]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS).
Medline ID 99313446
PubMed ID 10386874
Journal Protein Sci
Year 1999
Volume 8
Pages 1250-6
Authors Erskine PT, Newbold R, Roper J, Coker A, Warren MJ, Shoolingin-Jordan PM, Wood SP, Cooper JB
Title The Schiff base complex of yeast 5-aminolaevulinic acid dehydratase with laevulinic acid.
Related PDB 1ylv
Related UniProtKB P05373
[25]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
Medline ID 20207114
PubMed ID 10739915
Journal Acta Crystallogr D Biol Crystallogr
Year 2000
Volume 56
Pages 421-30
Authors Erskine PT, Duke EM, Tickle IJ, Senior NM, Warren MJ, Cooper JB
Title MAD analyses of yeast 5-aminolaevulinate dehydratase: their use in structure determination and in defining the metal-binding sites.
Related PDB 1qmk 1qml 1qnv
Related UniProtKB P05373
[26]
Resource
Comments
Medline ID
PubMed ID 10913315
Journal Biochemistry
Year 2000
Volume 39
Pages 9018-29
Authors Kervinen J, Dunbrack RL Jr, Litwin S, Martins J, Scarrow RC, Volin M, Yeung AT, Yoon E, Jaffe EK
Title Porphobilinogen synthase from pea: expression from an artificial gene, kinetic characterization, and novel implications for subunit interactions.
Related PDB
Related UniProtKB
[27]
Resource
Comments
Medline ID
PubMed ID 10712932
Journal Chem Biol
Year 2000
Volume 7
Pages 185-96
Authors Jarret C, Stauffer F, Henz ME, Marty M, Luond RM, Bobalova J, Schurmann P, Neier R
Title Inhibition of Escherichia coli porphobilinogen synthase using analogs of postulated intermediates.
Related PDB
Related UniProtKB
[28]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
Medline ID 21338255
PubMed ID 11444968
Journal Biochemistry
Year 2001
Volume 40
Pages 8227-36
Authors Kervinen J, Jaffe EK, Stauffer F, Neier R, Wlodawer A, Zdanov A
Title Mechanistic basis for suicide inactivation of porphobilinogen synthase by 4,7-dioxosebacic acid, an inhibitor that shows dramatic species selectivity.
Related PDB 1i8j
Related UniProtKB P15002
[29]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS).
Medline ID 21405508
PubMed ID 11513881
Journal FEBS Lett
Year 2001
Volume 503
Pages 196-200
Authors Erskine PT, Coates L, Newbold R, Brindley AA, Stauffer F, Wood SP, Warren MJ, Cooper JB, Shoolingin-Jordan PM, Neier R
Title The X-ray structure of yeast 5-aminolaevulinic acid dehydratase complexed with two diacid inhibitors.
Related PDB 1eb3 1gjp
Related UniProtKB P05373
[30]
Resource
Comments
Medline ID
PubMed ID 11032841
Journal J Biol Chem
Year 2001
Volume 276
Pages 1538-44
Authors Mitchell LW, Volin M, Martins J, Jaffe EK
Title Mechanistic implications of mutations to the active site lysine of porphobilinogen synthase.
Related PDB
Related UniProtKB
[31]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
Medline ID 21431818
PubMed ID 11545591
Journal J Mol Biol
Year 2001
Volume 312
Pages 133-41
Authors Erskine PT, Newbold R, Brindley AA, Wood SP, Shoolingin-Jordan PM, Warren MJ, Cooper JB
Title The x-ray structure of yeast 5-aminolaevulinic acid dehydratase complexed with substrate and three inhibitors.
Related PDB 1h7n 1h7o 1h7p 1h7r
Related UniProtKB P05373
[32]
Resource
Comments
Medline ID
PubMed ID 11275419
Journal Toxicol Lett
Year 2001
Volume 119
Pages 27-37
Authors Farina M, Folmer V, Bolzan RC, Andrade LH, Zeni G, Braga AL, Rocha JB
Title Selenoxides inhibit delta-aminolevulinic acid dehydratase.
Related PDB
Related UniProtKB
[33]
Resource
Comments
Medline ID
PubMed ID 12196142
Journal Biochem Soc Trans
Year 2002
Volume 30
Pages 584-90
Authors Shoolingin-Jordan PM, Spencer P, Sarwar M, Erskine PE, Cheung KM, Cooper JB, Norton EB
Title 5-Aminolaevulinic acid dehydratase: metals, mutants and mechanism.
Related PDB
Related UniProtKB
[34]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
Medline ID 22028088
PubMed ID 11909869
Journal J Biol Chem
Year 2002
Volume 277
Pages 19792-9
Authors Jaffe EK, Kervinen J, Martins J, Stauffer F, Neier R, Wlodawer A, Zdanov A
Title Species-specific inhibition of porphobilinogen synthase by 4-oxosebacic acid.
Related PDB 1l6s 1l6y
Related UniProtKB P15002
[35]
Resource
Comments
Medline ID
PubMed ID 12079382
Journal J Mol Biol
Year 2002
Volume 320
Pages 237-47
Authors Frere F, Schubert WD, Stauffer F, Frankenberg N, Neier R, Jahn D, Heinz DW
Title Structure of porphobilinogen synthase from Pseudomonas aeruginosa in complex with 5-fluorolevulinic acid suggests a double Schiff base mechanism.
Related PDB 1gzg
Related UniProtKB
[36]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.66 ANGSTROMS) OF MUTANT D139N.
Medline ID 22075365
PubMed ID 12777167
Journal Biochem J
Year 2003
Volume 373
Pages 733-8
Authors Erskine PT, Coates L, Butler D, Youell JH, Brindley AA, Wood SP, Warren MJ, Shoolingin-Jordan PM, Cooper JB
Title X-ray structure of a putative reaction intermediate of 5-aminolaevulinic acid dehydratase.
Related PDB 1ohl
Related UniProtKB Q59643
[37]
Resource
Comments
Medline ID
PubMed ID 12897770
Journal Nat Struct Biol
Year 2003
Volume 10
Pages 757-63
Authors Breinig S, Kervinen J, Stith L, Wasson AS, Fairman R, Wlodawer A, Zdanov A, Jaffe EK
Title Control of tetrapyrrole biosynthesis by alternate quaternary forms of porphobilinogen synthase.
Related PDB 1pv8
Related UniProtKB
[38]
Resource
Comments
Medline ID
PubMed ID 15327955
Journal J Mol Biol
Year 2004
Volume 342
Pages 563-70
Authors Coates L, Beaven G, Erskine PT, Beale SI, Avissar YJ, Gill R, Mohammed F, Wood SP, Shoolingin-Jordan P, Cooper JB
Title The X-ray structure of the plant like 5-aminolaevulinic acid dehydratase from Chlorobium vibrioforme complexed with the inhibitor laevulinic acid at 2.6 A resolution.
Related PDB 1w1z
Related UniProtKB
[39]
Resource
Comments
Medline ID
PubMed ID 15644204
Journal J Mol Biol
Year 2005
Volume 345
Pages 1059-70
Authors Frere F, Reents H, Schubert WD, Heinz DW, Jahn D
Title Tracking the evolution of porphobilinogen synthase metal dependence in vitro.
Related PDB 1w54 1w56 1w5m 1w5n 1w5o 1w5p 1w5q
Related UniProtKB
[40]
Resource
Comments
Medline ID
PubMed ID 16131755
Journal Acta Crystallogr D Biol Crystallogr
Year 2005
Volume 61
Pages 1222-6
Authors Erskine PT, Coates L, Newbold R, Brindley AA, Stauffer F, Beaven GD, Gill R, Coker A, Wood SP, Warren MJ, Shoolingin-Jordan PM, Neier R, Cooper JB
Title Structure of yeast 5-aminolaevulinic acid dehydratase complexed with the inhibitor 5-hydroxylaevulinic acid.
Related PDB 2c1h
Related UniProtKB
[41]
Resource
Comments
Medline ID
PubMed ID 16304458
Journal Acta Crystallogr D Biol Crystallogr
Year 2005
Volume 61
Pages 1594-8
Authors Coates L, Beaven G, Erskine PT, Beale SI, Wood SP, Shoolingin-Jordan PM, Cooper JB
Title Structure of Chlorobium vibrioforme 5-aminolaevulinic acid dehydratase complexed with a diacid inhibitor.
Related PDB 1w31
Related UniProtKB
[42]
Resource
Comments
Medline ID
PubMed ID 16819823
Journal Biochemistry
Year 2006
Volume 45
Pages 8243-53
Authors Frere F, Nentwich M, Gacond S, Heinz DW, Neier R, Frankenberg-Dinkel N
Title Probing the active site of Pseudomonas aeruginosa porphobilinogen synthase using newly developed inhibitors.
Related PDB 2c13 2c14 2c15 2c16 2c18 2c19
Related UniProtKB

Comments
(A) Exchange of double-bonded atoms; Schiff-base formation between Lys260 and P-side ALA substrate (see [17], [27] and [31]):
There are several subfamilies of the homologous enzymes, such as zinc-dependent (S00239, S00538 in EzCatDB), and zinc-independent (S00537, S00539) subfamilies. This enzyme belongs to zinc-independent subfamily.
Although this enzyme binds magnesium ion, it is not directly involved in catalysis. In contrast, a monovalent cation such as sodium ion seems to be involved in catalysis at some stages of the catalytic reaction (see [35]).
According to the literature [35] and [42], the reaction proceeds as follows:
(A) Exchange of double-bonded atoms; Schiff-base formation between Lys260 and P-side ALA substrate:
(B) Exchange of double-bonded atoms; Schiff-base formation between Lys205 and A-side ALA substrate:
(C) Isomerization; Shift of double-bond from N=C-C to N-C=C, forming an enamine intermediate at A-side:
(D) Addition (C-C bond formation):
(E) Exchange of double-bonded atoms; Exchange of Schiff-base (C-N bond formation & releasing Lys205):
(F) Eliminative double-bond formation (releasing Lys260):
(G) Isomerization; Shift of double-bonds from N=C-C=C-C to N-C=C-C=C:
However, although the first two reactions (A-B) and the last reaction (G) seem to be common to all the homologous enzymes (S00239, S00538, S00539 in EzCatDB), the rest of the reactions (D-G) have not been elucidated yet.
The detailed mechanism must be as follows:
(A1) Lys205 acts as a modulator to lower the pKa of the nucleophile Lys260.
(A2) Lys260 makes a nucleophilic attack on the carbonyl carbon of the substrate, ALA, at P-side, leading to formation of a tetrahedral carbinolamine transition-state. The carbinolamine oxygen of the transition-state is stabilized by the positive charge of Lys205.
(A3) Lys205 acts as a general acid to protonate the carbinolamine oxygen of the transition-state, leading to formation of hydroxyl group, and then acts as a general base to deprotonate the sidechain of Lys260.
(A4) The lone pair of the amine nitrogen of Lys260 makes a nucleophilic attack on the carbon atom of the carbinolamine transition-state, forming a Schiff-base. At the same time, Lys205 acts as a general acid to protonate the hydroxyl group of the carbinolamine, to facilitate the elimination of water molecule.
(B) Exchange of double-bonded atoms; Schiff-base formation between Lys205 and A-side ALA substrate:
(B1) Unprotonated sidechain of Lys205 acts as a nucleophile to attack on the carbonyl carbon of the substrate, ALA, at A-side, leading to formation of a carbinolamine transition-state.

Created Updated
2004-06-22 2009-02-26