|
CATH domain | Related DB codes (homologues) |
---|
3.20.20.70 : TIM Barrel | S00215,S00217,S00218,S00219,S00532,S00198,S00220,S00745,S00537,S00538,S00539,S00826,S00841,S00235,S00240,S00243,S00244,S00199,S00200,S00201,S00221,S00222,S00847,S00224,S00225,S00226,D00014,D00029,M00141,T00015,T00239,D00664,D00665,D00804,D00863,T00089 |
Enzyme Name | UniProtKB | KEGG |
---|
| P0ACB2 |
---|
Protein name | Delta-aminolevulinic acid dehydratase | porphobilinogen synthaseaminolevulinate dehydratasedelta-aminolevulinate dehydratasedelta-aminolevulinic acid dehydrasedelta-aminolevulinic acid dehydrataseaminolevulinic dehydratasedelta-aminolevulinic dehydratase5-levulinic acid dehydratase5-aminolevulinate hydro-lyase (adding 5-aminolevulinate andcyclizing) |
---|
Synonyms | ALADHALADEC 4.2.1.24Porphobilinogen synthase |
---|
RefSeq | NP_414903.4 (Protein) NC_000913.2 (DNA/RNA sequence) YP_488662.1 (Protein) NC_007779.1 (DNA/RNA sequence)
|
---|
Pfam | PF00490 (ALAD) [Graphical view]
|
---|
KEGG pathways | MAP code | Pathways |
---|
MAP00860 | Porphyrin and chlorophyll metabolism |
UniProtKB:Accession Number | P0ACB2 |
---|
Entry name | HEM2_ECOLI |
---|
Activity | 2 5-aminolevulinate = porphobilinogen + 2 H(2)O. |
---|
Subunit | Homooctamer. |
---|
Subcellular location |
|
---|
Cofactor | Binds 1 magnesium ion per monomer.,Binds 1 zinc ion per monomer. |
---|
Compound table: links to PDB-related databases & PoSSuM |
---|
| Cofactors | Substrates | Products | intermediates |
---|
KEGG-id | C00038 | C00305 | C00430 | C00931 | C00001 |
|
|
|
|
|
|
|
---|
Compound | Zinc | Magnesium | 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 | heavy metal | divalent metal (Ca2+, Mg2+) | amino acids,carbohydrate | amine group,aromatic ring (with nitrogen atoms),carboxyl group | H2O |
|
|
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|
|
|
---|
ChEBI | 29105
| 18420
| 17549 356416
| 17381
| 15377
|
|
|
|
|
|
|
|
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PubChem | 32051
| 888
| 137 7048523
| 1021
| 22247451 962
|
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|
|
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| | | | | | | | | | | | | | | | | | | |
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1b4eA |  |  |  |  |  |  |  | Bound:_ZN 400 | Analogue:_ZN 401 | Unbound | Unbound | | Unbound | Intermediate-analogue:LEA | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1i8jA |  |  |  |  |  |  |  | Bound:_ZN | Bound:_MG | Unbound | Unbound | | Unbound | Unbound | Unbound | Intermediate-analogue:DSB | Unbound | Unbound | Unbound |
---|
1i8jB |  |  |  |  |  |  |  | Bound:_ZN | Bound:_MG | Unbound | Unbound | | Unbound | Unbound | Unbound | Intermediate-analogue:DSB | Unbound | Unbound | Unbound |
---|
1l6sA |  |  |  |  |  |  |  | Bound:_ZN | Bound:_MG | Unbound | Unbound | | Unbound | Unbound | Unbound | Intermediate-analogue:DSB | Unbound | Unbound | Unbound |
---|
1l6sB |  |  |  |  |  |  |  | Bound:_ZN | Bound:_MG | Unbound | Unbound | | Unbound | Unbound | Unbound | Intermediate-analogue:DSB | Unbound | Unbound | Unbound |
---|
1l6yA |  |  |  |  |  |  |  | Bound:_ZN | Bound:_MG | Unbound | Unbound | | Unbound | Intermediate-analogue:4OX | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
1l6yB |  |  |  |  |  |  |  | Bound:_ZN | Bound:_MG | Unbound | Unbound | | Unbound | Intermediate-analogue:4OX | Unbound | Unbound | Unbound | Unbound | Unbound |
---|
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] |
---|
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. |
---|
[2] |
---|
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. |
---|
[3] |
---|
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. |
---|
[4] |
---|
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). |
---|
[5] |
---|
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. |
---|
[6] |
---|
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. |
---|
[7] |
---|
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. |
---|
[8] |
---|
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). |
---|
[9] |
---|
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 UniProtKB | P15002 |
---|
[10] |
---|
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. |
---|
[11] |
---|
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). |
---|
[12] |
---|
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. |
---|
[13] |
---|
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. |
---|
[14] |
---|
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. |
---|
[15] |
---|
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'. |
---|
[16] |
---|
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. |
---|
[17] |
---|
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] |
---|
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. |
---|
[19] |
---|
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. |
---|
[20] |
---|
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] |
---|
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. |
---|
[22] |
---|
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. |
---|
[23] |
---|
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] |
---|
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] |
---|
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] |
---|
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. |
---|
[27] |
---|
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. |
---|
[28] |
---|
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] |
---|
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] |
---|
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. |
---|
[31] |
---|
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] |
---|
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. |
---|
[33] |
---|
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. |
---|
[34] |
---|
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] |
---|
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 |
---|
[36] |
---|
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] |
---|
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 |
---|
[38] |
---|
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 |
---|
[39] |
---|
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 |
---|
[40] |
---|
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 |
---|
[41] |
---|
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 |
---|
[42] |
---|
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. |
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Related PDB | 2c13,2c14,2c15,2c16,2c18,2c19 |
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comments | 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-dependent subfamily. According to the literature [36], the reaction proceeds as follows: (A) Exchange of double-bonded atoms; Schiff-base formation between Lys246 and P-side ALA substrate: (B) Exchange of double-bonded atoms; Schiff-base formation between Lys194 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) Addition (C-N bond formation): (F) Eliminative double-bond formation (releasing Lys194 at A-side): (G) Eliminative double-bond formation (releasing Lys246 at P-side): (H) 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 (H) seem to be common to all the homologous enzymes (S00537, S00538, S00539 in EzCatDB), the rest of the reactions (D-G) have not been elucidated yet. The detailed mechanism must be as follows: (A) Exchange of double-bonded atoms; Schiff-base formation between Lys246 and P-side ALA substrate (see [17], [27] and [31]): (A1) Lys194 acts as a modulator to lower the pKa of the nucleophile Lys246. (A2) Lys246 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 Lys194. (A3) Lys194 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 Lys246. (A4) The lone pair of the amine nitrogen of Lys246 makes a nucleophilic attack on the carbon atom of the carbinolamine transition-state, forming a Schiff-base. At the same time, Lys194 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 Lys194 and A-side ALA substrate: (B1) Unprotonated sidechain of Lys194 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. The carbinolamine oxygen of the transition-state is stabilized by the positive charge of the amino group of the ALA substrate at A-side. (B2) The amino group of the ALA substrate at A-side might act as a general acid to protonate the carbinolamine oxygen of the transition-state, leading to formation of hydroxyl group, and then act as a general base to deprotonate the sidechain of Lys194. (B3) The lone pair of the amine nitrogen of Lys194 makes a nucleophilic attack on the carbon atom of the carbinolamine transition-state, forming a Schiff-base. At the same time, the amino group of the ALA acts as a general acid to protonate the hydroxyl group of the carbinolamine, to facilitate the elimination of water molecule. (C) Isomerization; Shift of double-bond from N=C-C to N-C=C, forming an enamine intermediate at A-side: (C1) Hydroxide bound to zinc ion acts as a strong base to deprotonate C3 methylene of the Schiff-base intermediate at A-side, leading to formation of an enamine intermediate. (E) Addition (C-N bond formation): (E1) The unprotonated amino group of the ALA at A-side acts as a general base to deprotonate the amino group of the ALA at P-side. (E2) The amino group of the ALA at P-side makes a nucleophilic attack on the Schiff base of A-side, forming a cyclic intermediate. (E3) The protonated amino group of the ALA at A-side acts as a general acid to protonate the sidechain amine group of Lys194 at A-side. (F) Eliminative double-bond formation (releasing Lys194 at A-side): (F1) Lys246, which is covalently bound to the cyclic intermediate, acts as a general base to deprotonate the C2 atom of the intermediate (or originally C3 atom of ALA at A-side), and then acts as a general acid to protonate the eliminated group, Lys210. (F2) At the same time, Lys210 is eliminated from the intermediate; E2-like reaction. (G) Eliminative double-bond formation (releasing Lys246 at P-side): (G1) Lys210 acts as a general acid to protonate the eliminated group, the amino group of Lys246. (G2) The lone pair of enamine of the intermediate push the electron to form a new double bond, facilitating the elimination of Lys246; E1-like reaction. (H) Isomerization; Shift of double-bonds from N=C-C=C-C to N-C=C-C=C: (H1) Electrophilic Schiff-base assisted reaction. Lys246 acts as a general base to the C4 methylene of the intermediate (or originally C5 atom of ALA at P-side), leading to the shift of double-bonds.
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created | updated |
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2004-06-22 | 2010-05-19 |
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