DB code: S00240

RLCP classification 6.10.448000.112 : Double-bonded atom exchange
5.10.12500.6010 : Elimination
6.20.28500.6010 : Double-bonded atom exchange
CATH domain 3.20.20.70 : TIM Barrel Catalytic domain
E.C. 4.2.1.10
CSA 1qfe
M-CSA 1qfe
MACiE M0054

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 S00239 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
P24670 3-dehydroquinate dehydratase
3-dehydroquinase
EC 4.2.1.10
Type I DHQase
NP_805037.1 (Protein)
NC_004631.1 (DNA/RNA sequence)
PF01487 (DHquinase_I)
[Graphical View]

KEGG enzyme name
3-dehydroquinate dehydratase
3-dehydroquinate hydrolase
DHQase
dehydroquinate dehydratase
3-dehydroquinase
5-dehydroquinase
dehydroquinase
5-dehydroquinate dehydratase
5-dehydroquinate hydro-lyase
3-dehydroquinate hydro-lyase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P24670 AROD_SALTI 3-dehydroquinate = 3-dehydroshikimate + H(2)O. Homodimer.

KEGG Pathways
Map code Pathways E.C.
MAP00400 Phenylalanine, tyrosine and tryptophan biosynthesis

Compound table
Substrates Products Intermediates
KEGG-id C00944 C02637 C00001
E.C.
Compound 3-Dehydroquinate 3-Dehydroshikimate H2O
Type carbohydrate,carboxyl group carbohydrate,carboxyl group H2O
ChEBI 17947
30918
15377
PubChem 439351
439774
22247451
962
1qfeA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Intermediate-bound:DHS
1qfeB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Intermediate-bound:DHS
1l9wA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Intermediate-bound:DHS
1l9wB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Intermediate-bound:DHS
1l9wC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Intermediate-bound:DHS
1l9wD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Intermediate-bound:DHS
1gqnA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P24670 & literature [9]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1qfeA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 86;HIS 143;LYS 170
1qfeB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 86;HIS 143;LYS 170
1l9wA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 86;HIS 143;LYS 170
1l9wB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 86;HIS 143;LYS 170
1l9wC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 86;HIS 143;LYS 170
1l9wD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 86;HIS 143;LYS 170
1gqnA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain GLU 86;HIS 143;LYS 170

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
Fig.1, p.22242 5
[6]
SCHEME 1 5
[7]
SCHEME 1, SCHEME 2, p.25834-25835 9
[9]
Fig.1 3
[10]
Scheme 1 4

References
[1]
Resource
Comments
Medline ID
PubMed ID 1554351
Journal Biochem J
Year 1992
Volume 282
Pages 687-95
Authors Kleanthous C, Deka R, Davis K, Kelly SM, Cooper A, Harding SE, Price NC, Hawkins AR, Coggins JR
Title A comparison of the enzymological and biophysical properties of two distinct classes of dehydroquinase enzymes.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 1429576
Journal J Biol Chem
Year 1992
Volume 267
Pages 22237-42
Authors Deka RK, Kleanthous C, Coggins JR
Title Identification of the essential histidine residue at the active site of Escherichia coli dehydroquinase.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 1522599
Journal J Mol Biol
Year 1992
Volume 227
Pages 352-5
Authors Boys CW, Bury SM, Sawyer L, Moore JD, Charles IG, Hawkins AR, Deka R, Kleanthous C, Coggins JR
Title Crystallization of a type I 3-dehydroquinase from Salmonella typhi.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 8216229
Journal Biochem J
Year 1993
Volume 295
Pages 277-85
Authors Moore JD, Hawkins AR, Charles IG, Deka R, Coggins JR, Cooper A, Kelly SM, Price NC
Title Characterization of the type I dehydroquinase from Salmonella typhi.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 8050603
Journal FEBS Lett
Year 1994
Volume 349
Pages 397-402
Authors Deka RK, Anton IA, Dunbar B, Coggins JR
Title The characterisation of the shikimate pathway enzyme dehydroquinase from Pisum sativum.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 8119885
Journal J Biol Chem
Year 1994
Volume 269
Pages 5523-6
Authors Reilly A, Morgan P, Davis K, Kelly SM, Greene J, Rowe AJ, Harding SE, Price NC, Coggins JR, Kleanthous C
Title Product-induced stabilization of tertiary and quaternary structure in Escherichia coli dehydroquinase.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 7592767
Journal J Biol Chem
Year 1995
Volume 270
Pages 25827-36
Authors Leech AP, James R, Coggins JR, Kleanthous C
Title Mutagenesis of active site residues in type I dehydroquinase from Escherichia coli. Stalled catalysis in a histidine to alanine mutant.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 9545291
Journal J Biol Chem
Year 1998
Volume 273
Pages 9602-7
Authors Leech AP, Boetzel R, McDonald C, Shrive AK, Moore GR, Coggins JR, Sawyer L, Kleanthous C
Title Re-evaluating the role of His-143 in the mechanism of type I dehydroquinase from Escherichia coli using two-dimensional 1H,13C NMR.
Related PDB
Related UniProtKB
[9]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10360352
Journal Nat Struct Biol
Year 1999
Volume 6
Pages 521-5
Authors Gourley DG, Shrive AK, Polikarpov I, Krell T, Coggins JR, Hawkins AR, Isaacs NW, Sawyer L
Title The two types of 3-dehydroquinase have distinct structures but catalyze the same overall reaction.
Related PDB 1qfe
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 10698442
Journal Bioorg Med Chem Lett
Year 2000
Volume 10
Pages 231-4
Authors Parker EJ, Gonzalez Bello C, Coggins JR, Hawkins AR, Abell C
Title Mechanistic studies on type I and type II dehydroquinase with (6R)- and (6S)-6-fluoro-3-dehydroquinic acids.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 11976491
Journal Acta Crystallogr D Biol Crystallogr
Year 2002
Volume 58
Pages 798-804
Authors Lee WH, Perles LA, Nagem RA, Shrive AK, Hawkins A, Sawyer L, Polikarpov I
Title Comparison of different crystal forms of 3-dehydroquinase from Salmonella typhi and its implication for the enzyme activity.
Related PDB 1l9w 1gqn
Related UniProtKB

Comments
The catalytic mechanism of this enzyme involves Schiff-base formation by Lys170 with the substrate. This enzyme catalyzes three successive reactions;
(A) Schiff-base formation (elimination of hydroxyl group),
(B) elimination of hydroxyl group,
(C) Schiff-base deformation (water addition or hydration).
These reactions proceeds in the following way.
(A) The Schiff-base forming reaction is actually composed of addition reaction and elimination reaction. The Schiff-base forming reaction proceeds as follows (see [2], [7], [8] & [9]):
(A1) Lys170 makes a nucleophilic attack on the C3 carbonyl carbon, forming a tetrahedral intermediate.
(A2) A proton atom on the amine of Lys170 moves to the oxygen on the tetrahedral intermediate, forming a hydroxyl group. (Lys170 plays a dual role as nucleophile-acid.)
(A3) The lone pair on the nitrogen atom of Lys170 attacks on the C3 carbon atom. The hydroxyl group is protonated by the second general acid, leading to the elimination of a water and the Schiff-base formation. According to the literature [7], His143 acts as the second general acid.
(B) The hydroxyl elimination reaction proceeds as follows (see [2], [8] & [9]):
(B1) The first general base abstracts a proton from the C2 carbon atom, forming a carbanion intermediate. This intermediate is a tautomer between the two forms. One is the Schiff-base form, and another has a double-bond between the C2 and C3 carbons with an amine group at Lys170. (According to the literature [9], His143 acts as the base.)
(B2) The lone pair of the amine at the latter intermediate attacks on the C2 carbon, leading to the formation of a double-bond between the C1 and C2 atoms and the elimination of the hydroxyl group at the C1. This elimination is assisted by the protonation to the hydroxyl group by the general acid. According to the literature [2] & [7], His143 acts as the general acid.
(C) The Schiff-base deforming reaction is also composed of addition reaction and elimination reaction. The Shciff-base deforming reaction proceeds as follows (see [2], [7], [8] & [9]):
(C1) The first general base activates a water molecule, by abstracting a proton from the water. This activated water makes a nucleophilic attack on the Schiff-base carbon, to form a tetrahedral intermediate, again.
(C2) The amine group of Lys170 deprotonates the hydroxyl group, forming an oxygen anion. This anion makes an attack on the C2 atom, leading to the formation of the carbonyl group and the release of Lys170 from the C2 atom.
According to the literature [9], Glu86 plays an important role in orienting His143 in proper positions.

Created Updated
2004-06-28 2009-02-26