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 17947	30918 30918	15377 15377
PubChem	439351 439351	439774 439774	22247451 962 22247451 962

1qfeA	Unbound	Unbound		Intermediate-bound:DHS
1qfeB	Unbound	Unbound		Intermediate-bound:DHS
1l9wA	Unbound	Unbound		Intermediate-bound:DHS
1l9wB	Unbound	Unbound		Intermediate-bound:DHS
1l9wC	Unbound	Unbound		Intermediate-bound:DHS
1l9wD	Unbound	Unbound		Intermediate-bound:DHS
1gqnA	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	GLU 86;HIS 143;LYS 170
1qfeB	GLU 86;HIS 143;LYS 170
1l9wA	GLU 86;HIS 143;LYS 170
1l9wB	GLU 86;HIS 143;LYS 170
1l9wC	GLU 86;HIS 143;LYS 170
1l9wD	GLU 86;HIS 143;LYS 170
1gqnA	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.

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