EzCatDB: S00240

DB codeS00240
RLCP classification6.10.448000.112
5.10.12500.6010
6.20.28500.6010
CATH domainDomain 13.20.20.70Catalytic domain
E.C.4.2.1.10
CSA1qfe
MACiEM0054

CATH domainRelated DB codes (homologues)
3.20.20.70S00215,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

Enzyme Name
Swiss-protKEGG

P24670
Protein name3-dehydroquinate dehydratase3-dehydroquinate dehydratase
3-dehydroquinate hydrolase
DHQase
dehydroquinate dehydratase
3-dehydroquinase
5-dehydroquinase
dehydroquinase
5-dehydroquinate dehydratase
5-dehydroquinate hydro-lyase
3-dehydroquinate hydro-lyase
Synonyms3-dehydroquinase
EC 4.2.1.10
Type I DHQase

KEGG pathways
MAP codePathways
MAP00400Phenylalanine, tyrosine and tryptophan biosynthesis

Swiss-prot:Accession NumberP24670
Entry nameAROD_SALTI
Activity3-dehydroquinate = 3-dehydroshikimate + H(2)O.
SubunitHomodimer.
Subcellular location
Cofactor


SubstratesProductsintermediates
KEGG-idC00944C02637C00001
Compound3-Dehydroquinate3-DehydroshikimateH2O
Typecarbohydrate,carboxyl groupcarbohydrate,carboxyl groupH2O
1qfeAUnboundUnbound
Intermediate-bound:DHS
1qfeBUnboundUnbound
Intermediate-bound:DHS
1l9wAUnboundUnbound
Intermediate-bound:DHS
1l9wBUnboundUnbound
Intermediate-bound:DHS
1l9wCUnboundUnbound
Intermediate-bound:DHS
1l9wDUnboundUnbound
Intermediate-bound:DHS
1gqnAUnboundUnbound
Unbound

Active-site residues
resource
Swiss-prot;P24670 & literature [9]
pdbCatalytic residues
1qfeAGLU 86;HIS 143;LYS 170
1qfeBGLU 86;HIS 143;LYS 170
1l9wAGLU 86;HIS 143;LYS 170
1l9wBGLU 86;HIS 143;LYS 170
1l9wCGLU 86;HIS 143;LYS 170
1l9wDGLU 86;HIS 143;LYS 170
1gqnAGLU 86;HIS 143;LYS 170

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]Fig.1, p.222425
[6]SCHEME 15
[7]SCHEME 1, SCHEME 2, p.25834-258359
[9]Fig.13
[10]Scheme 14

references
[1]
PubMed ID1554351
JournalBiochem J
Year1992
Volume282
Pages687-95
AuthorsKleanthous C, Deka R, Davis K, Kelly SM, Cooper A, Harding SE, Price NC, Hawkins AR, Coggins JR
TitleA comparison of the enzymological and biophysical properties of two distinct classes of dehydroquinase enzymes.
[2]
PubMed ID1429576
JournalJ Biol Chem
Year1992
Volume267
Pages22237-42
AuthorsDeka RK, Kleanthous C, Coggins JR
TitleIdentification of the essential histidine residue at the active site of Escherichia coli dehydroquinase.
[3]
PubMed ID1522599
JournalJ Mol Biol
Year1992
Volume227
Pages352-5
AuthorsBoys CW, Bury SM, Sawyer L, Moore JD, Charles IG, Hawkins AR, Deka R, Kleanthous C, Coggins JR
TitleCrystallization of a type I 3-dehydroquinase from Salmonella typhi.
[4]
PubMed ID8216229
JournalBiochem J
Year1993
Volume295
Pages277-85
AuthorsMoore JD, Hawkins AR, Charles IG, Deka R, Coggins JR, Cooper A, Kelly SM, Price NC
TitleCharacterization of the type I dehydroquinase from Salmonella typhi.
[5]
PubMed ID8050603
JournalFEBS Lett
Year1994
Volume349
Pages397-402
AuthorsDeka RK, Anton IA, Dunbar B, Coggins JR
TitleThe characterisation of the shikimate pathway enzyme dehydroquinase from Pisum sativum.
[6]
PubMed ID8119885
JournalJ Biol Chem
Year1994
Volume269
Pages5523-6
AuthorsReilly A, Morgan P, Davis K, Kelly SM, Greene J, Rowe AJ, Harding SE, Price NC, Coggins JR, Kleanthous C
TitleProduct-induced stabilization of tertiary and quaternary structure in Escherichia coli dehydroquinase.
[7]
PubMed ID7592767
JournalJ Biol Chem
Year1995
Volume270
Pages25827-36
AuthorsLeech AP, James R, Coggins JR, Kleanthous C
TitleMutagenesis of active site residues in type I dehydroquinase from Escherichia coli. Stalled catalysis in a histidine to alanine mutant.
[8]
PubMed ID9545291
JournalJ Biol Chem
Year1998
Volume273
Pages9602-7
AuthorsLeech AP, Boetzel R, McDonald C, Shrive AK, Moore GR, Coggins JR, Sawyer L, Kleanthous C
TitleRe-evaluating the role of His-143 in the mechanism of type I dehydroquinase from Escherichia coli using two-dimensional 1H,13C NMR.
[9]
CommentsX-ray crystallography
PubMed ID10360352
JournalNat Struct Biol
Year1999
Volume6
Pages521-5
AuthorsGourley DG, Shrive AK, Polikarpov I, Krell T, Coggins JR, Hawkins AR, Isaacs NW, Sawyer L
TitleThe two types of 3-dehydroquinase have distinct structures but catalyze the same overall reaction.
Related PDB1qfe
[10]
PubMed ID10698442
JournalBioorg Med Chem Lett
Year2000
Volume10
Pages231-4
AuthorsParker EJ, Gonzalez Bello C, Coggins JR, Hawkins AR, Abell C
TitleMechanistic studies on type I and type II dehydroquinase with (6R)- and (6S)-6-fluoro-3-dehydroquinic acids.
[11]
PubMed ID11976491
JournalActa Crystallogr D Biol Crystallogr
Year2002
Volume58
Pages798-804
AuthorsLee WH, Perles LA, Nagem RA, Shrive AK, Hawkins A, Sawyer L, Polikarpov I
TitleComparison of different crystal forms of 3-dehydroquinase from Salmonella typhi and its implication for the enzyme activity.
Related PDB1l9w,1gqn

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.

createdupdated
2004-06-282009-02-26
Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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