DB code: D00261

RLCP classification 8.131.712490.370 : Isomerization
5.14.3200000.372 : Elimination
8.113.901890.372 : Isomerization
CATH domain 3.30.390.10 : Enolase-like; domain 1
3.20.20.120 : TIM Barrel Catalytic domain
E.C. 4.2.1.40
CSA 1ec9
M-CSA 1ec9
MACiE

CATH domain Related DB codes (homologues)
3.20.20.120 : TIM Barrel D00273 D00282 D00283
3.30.390.10 : Enolase-like; domain 1 D00273 D00282 D00283

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam RefSeq
P42206 Glucarate dehydratase
GDH
GlucD
EC 4.2.1.40
PF01188 (MR_MLE)
PF02746 (MR_MLE_N)
[Graphical View]
P0AES2 Glucarate dehydratase
GDH
GlucD
EC 4.2.1.40
PF01188 (MR_MLE)
[Graphical View]
NP_417267.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_490995.1 (Protein)
NC_007779.1 (DNA/RNA sequence)

KEGG enzyme name
glucarate dehydratase
D-glucarate dehydratase
D-glucarate hydro-lyase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P42206 GUDH_PSEPU D-glucarate = 5-dehydro-4-deoxy-D-glucarate + H(2)O. Homotetramer. Magnesium (By similarity).
P0AES2 GUDH_ECOLI D-glucarate = 5-dehydro-4-deoxy-D-glucarate + H(2)O. Magnesium.

KEGG Pathways
Map code Pathways E.C.
MAP00053 Ascorbate and aldarate metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00818 C00679 C00001 I00072 I00073
E.C.
Compound Magnesium D-Glucarate 5-Dehydro-4-deoxy-D-glucarate H2O 5,6-enediol-D-glucarate 4,5-enol-4-deoxy-D-glucarate
Type divalent metal (Ca2+, Mg2+) carbohydrate,carboxyl group carbohydrate,carboxyl group H2O
ChEBI 18420
16002
16369
15377
PubChem 888
33037
607
439290
22247451
962
1bqgA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1ec7A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1ec7B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1ec7C01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1ec7D01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1ec8A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1ec8B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1ec8C01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1ec8D01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1ec9A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1ec9B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1ec9C01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1ec9D01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1ecqA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1ecqB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1ecqC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1ecqD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1jctA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1jctB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1jdfA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1jdfB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1jdfC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1jdfD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1bqgA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1ec7A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Unbound Unbound Unbound Unbound
1ec7B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Unbound Unbound Unbound Unbound
1ec7C02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Unbound Unbound Unbound Unbound
1ec7D02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Unbound Unbound Unbound Unbound
1ec8A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Unbound Bound:GLR Unbound Unbound
1ec8B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Unbound Bound:GLR Unbound Unbound
1ec8C02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Unbound Bound:GLR Unbound Unbound
1ec8D02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Unbound Bound:GLR Unbound Unbound
1ec9A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Unbound Unbound Intermediate-analogue:XYH Unbound
1ec9B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Unbound Unbound Intermediate-analogue:XYH Unbound
1ec9C02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Unbound Unbound Intermediate-analogue:XYH Unbound
1ec9D02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Unbound Unbound Intermediate-analogue:XYH Unbound
1ecqA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Unbound Unbound Unbound Intermediate-bound:DXG
1ecqB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Unbound Unbound Unbound Intermediate-bound:DXG
1ecqC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Unbound Unbound Unbound Intermediate-bound:DXG
1ecqD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Unbound Unbound Unbound Intermediate-bound:DXG
1jctA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Bound:GKR Unbound Unbound Unbound
1jctB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Bound:GKR Unbound Unbound Unbound
1jdfA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Unbound Bound:GLR Unbound Unbound
1jdfB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Unbound Bound:GLR Unbound Unbound
1jdfC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Unbound Bound:GLR Unbound Unbound
1jdfD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Unbound Bound:GLR Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [2], [4], [5]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1bqgA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ec7A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ec7B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ec7C01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ec7D01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ec8A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ec8B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ec8C01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ec8D01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ec9A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ec9B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ec9C01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ec9D01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ecqA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ecqB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ecqC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ecqD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1jctA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1jctB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1jdfA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1jdfB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1jdfC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1jdfD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1bqgA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 156;LYS 213;ASP 319;HIS 345 ASP 241;GLU 266;ASN 295(Magnesium binding)
1ec7A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 150;LYS 207;ASP 313;HIS 339 ASP 235;GLU 260;ASN 289(Magnesium binding)
1ec7B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 150;LYS 207;ASP 313;HIS 339 ASP 235;GLU 260;ASN 289(Magnesium binding)
1ec7C02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 150;LYS 207;ASP 313;HIS 339 ASP 235;GLU 260;ASN 289(Magnesium binding)
1ec7D02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 150;LYS 207;ASP 313;HIS 339 ASP 235;GLU 260;ASN 289(Magnesium binding)
1ec8A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 150;LYS 207;ASP 313;HIS 339 ASP 235;GLU 260;ASN 289(Magnesium binding)
1ec8B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 150;LYS 207;ASP 313;HIS 339 ASP 235;GLU 260;ASN 289(Magnesium binding)
1ec8C02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 150;LYS 207;ASP 313;HIS 339 ASP 235;GLU 260;ASN 289(Magnesium binding)
1ec8D02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 150;LYS 207;ASP 313;HIS 339 ASP 235;GLU 260;ASN 289(Magnesium binding)
1ec9A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 150;LYS 207;ASP 313;HIS 339 ASP 235;GLU 260;ASN 289(Magnesium binding)
1ec9B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 150;LYS 207;ASP 313;HIS 339 ASP 235;GLU 260;ASN 289(Magnesium binding)
1ec9C02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 150;LYS 207;ASP 313;HIS 339 ASP 235;GLU 260;ASN 289(Magnesium binding)
1ec9D02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 150;LYS 207;ASP 313;HIS 339 ASP 235;GLU 260;ASN 289(Magnesium binding)
1ecqA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 150;LYS 207;ASP 313;HIS 339 ASP 235;GLU 260;ASN 289(Magnesium binding)
1ecqB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 150;LYS 207;ASP 313;HIS 339 ASP 235;GLU 260;ASN 289(Magnesium binding)
1ecqC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 150;LYS 207;ASP 313;HIS 339 ASP 235;GLU 260;ASN 289(Magnesium binding)
1ecqD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 150;LYS 207;ASP 313;HIS 339 ASP 235;GLU 260;ASN 289(Magnesium binding)
1jctA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 150;LYS 207;ASP 313;HIS 339 ASP 235;GLU 260;ASN 289(Magnesium binding) mutant N341L
1jctB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 150;LYS 207;ASP 313;HIS 339 ASP 235;GLU 260;ASN 289(Magnesium binding) mutant N341L
1jdfA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 150;LYS 207;ASP 313;HIS 339 ASP 235;GLU 260;ASN 289(Magnesium binding) mutant N341D
1jdfB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 150;LYS 207;ASP 313;HIS 339 ASP 235;GLU 260;ASN 289(Magnesium binding) mutant N341D
1jdfC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 150;LYS 207;ASP 313;HIS 339 ASP 235;GLU 260;ASN 289(Magnesium binding) mutant N341D
1jdfD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain TYR 150;LYS 207;ASP 313;HIS 339 ASP 235;GLU 260;ASN 289(Magnesium binding) mutant N341D

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
p.16496
[2]
Scheme 2, p.14365-14367 4
[4]
Scheme 1, p.4596-4601 3
[5]
Scheme 1, p.10058 3

References
[1]
Resource
Comments
Medline ID
PubMed ID 8987982
Journal Biochemistry
Year 1996
Volume 35
Pages 16489-501
Authors Babbitt PC, Hasson MS, Wedekind JE, Palmer DR, Barrett WC, Reed GH, Rayment I, Ringe D, Kenyon GL, Gerlt JA
Title The enolase superfamily: a general strategy for enzyme-catalyzed abstraction of the alpha-protons of carboxylic acids.
Related PDB
Related UniProtKB
[2]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 9772161
Journal Biochemistry
Year 1998
Volume 37
Pages 14358-68
Authors Gulick AM, Palmer DR, Babbitt PC, Gerlt JA, Rayment I
Title Evolution of enzymatic activities in the enolase superfamily: crystal structure of (D)-glucarate dehydratase from Pseudomonas putida.
Related PDB 1bqg
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 9772160
Journal Biochemistry
Year 1998
Volume 37
Pages 14350-7
Authors Palmer DR, Hubbard BK, Gerlt JA
Title Evolution of enzymatic activities in the enolase superfamily: partitioning of reactive intermediates by (D)-glucarate dehydratase from Pseudomonas putida.
Related PDB
Related UniProtKB
[4]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS)
Medline ID 98447506
PubMed ID 10769114
Journal Biochemistry
Year 2000
Volume 39
Pages 4590-602
Authors Gulick AM, Hubbard BK, Gerlt JA, Rayment I
Title Evolution of enzymatic activities in the enolase superfamily: crystallographic and mutagenesis studies of the reaction catalyzed by D-glucarate dehydratase from Escherichia coli.
Related PDB 1ec7 1ec8 1ec9 1ecq
Related UniProtKB P42206
[5]
Resource
Comments
Medline ID
PubMed ID 11513584
Journal Biochemistry
Year 2001
Volume 40
Pages 10054-62
Authors Gulick AM, Hubbard BK, Gerlt JA, Rayment I
Title Evolution of enzymatic activities in the enolase superfamily: identification of the general acid catalyst in the active site of D-glucarate dehydratase from Escherichia coli.
Related PDB 1jct 1jdf
Related UniProtKB

Comments
This enzyme belongs to the enolase superfamily.
This enzyme catalyzes dehydration of either D-glucarate or L-idarate to form 5-Dehydro-4-deoxy-D-glucarate (KDG).
According to the literature [2], [4] & [5], the catalytic reaction proceeds as follows:
(A) Isomerization (change in the position of double-bond):
(A1) A general base abstracts the alpha-proton from the C5 carbon, resulting in the formation of the enediolate anion intermediate. Here, His339 (of 1ec7) acts as the R-specific base for the D-glucarate substrate, whilst Lys207 acts as the S-specific base for the L-idarate (see [4] & [5]).
(A2) The enediolate anion is stabilized by the manesium ion, which is coordinated by Asp235, Glu266 and Asn289.
(B) Elimination of hydroxyl group from the substrate:
(B1) A general acid eliminates the 4-OH group from the enediolate anion intermediate, by donating a proton to the group, resulting in the formation of an enol intermediate, in which a double bond is formed between the C4 and the C5 carbon atoms. Although the earlier paper [3] mentioned that Tyr150 may act as the general acid, more recent papers [4] & [5] proposed that His339 would act as the general acid.
(B2) The enol intermediate might be stabilized by Tyr150, Lys205 and Asn237, as well as the magnesium ion (see [4]). The enol oxygen is stabilized by Tyr150, whereas the carboxylate is stabilized by Lys205, Asn237 and the magnesium ion.
(C) Isomerization (change in the position of double-bond):
(C0) The enol oxygen is stabilized by Tyr150, whereas the carboxylate is stabilized by Lys205, Asn237 and the magnesium ion.
(C1) Another general acid donates a proton to the C4 carbon of the enol intermediate, leading to its tautomerization and to the final product, KDG. According to the paper [5], His339 acts as the second acid, as well.

Created Updated
2004-07-01 2011-06-06