DB code: D00643

RLCP classification 3.103.70810.363 : Transfer
CATH domain 3.30.420.40 : Nucleotidyltransferase; domain 5
3.40.367.20 : Hexokinase; domain 1 Catalytic domain
E.C. 2.7.1.2
CSA 1q18
M-CSA 1q18
MACiE

CATH domain Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P0A6V8 Glucokinase
EC 2.7.1.2
Glucose kinase
NP_416889.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_490630.1 (Protein)
NC_007779.1 (DNA/RNA sequence)
PF02685 (Glucokinase)
[Graphical View]
Q4E4E1
Glucokinase 1, putative
EC 2.7.1.2
XP_821474.1 (Protein)
XM_816381.1 (DNA/RNA sequence)
PF02685 (Glucokinase)
[Graphical View]

KEGG enzyme name
Glucokinase
Glucokinase (phosphorylating)

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P0A6V8 GLK_ECOLI ATP + D-glucose = ADP + D-glucose 6-phosphate. Cytoplasm.
Q4E4E1 Q4E4E1_TRYCR

KEGG Pathways
Map code Pathways E.C.
MAP00010 Glycolysis / Gluconeogenesis
MAP00052 Galactose metabolism
MAP00500 Starch and sucrose metabolism
MAP00520 Amino sugar and nucleotide sugar metabolism
MAP00521 Streptomycin biosynthesis
MAP01061 Biosynthesis of phenylpropanoids
MAP01062 Biosynthesis of terpenoids and steroids
MAP01063 Biosynthesis of alkaloids derived from shikimate pathway
MAP01064 Biosynthesis of alkaloids derived from ornithine, lysine and nicotinic acid
MAP01065 Biosynthesis of alkaloids derived from histidine and purine
MAP01066 Biosynthesis of alkaloids derived from terpenoid and polyketide
MAP01070 Biosynthesis of plant hormones

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00002 C00031 C00008 C00092
E.C.
Compound Magnesium ATP D-glucose ADP D-glucose 6-phosphate
Type divalent metal (Ca2+, Mg2+) amine group,nucleotide carbohydrate amine group,nucleotide carbohydrate,phosphate group/phosphate ion
ChEBI 18420
 18420
 		15422
 15422
 		4167
 4167
 		16761
 16761
 		4170
 4170
PubChem 888
 888
 		5957
 5957
 		5793
 5793
 		6022
 6022
 		5958
 5958
1q18A01 Unbound Unbound Unbound Unbound Unbound
1q18B01 Unbound Unbound Unbound Unbound Unbound
1sz2A01 Unbound Unbound Unbound Unbound Unbound
1sz2B01 Unbound Unbound Unbound Unbound Unbound
2q2rA01 Unbound Unbound Unbound Unbound Unbound
2q2rB01 Unbound Unbound Unbound Unbound Unbound
1q18A02 Unbound Unbound Unbound Unbound Unbound
1q18B02 Unbound Unbound Unbound Unbound Unbound
1sz2A02 Unbound Unbound Bound:BGC Unbound Unbound
1sz2B02 Unbound Unbound Bound:BGC Unbound Unbound
2q2rA02 Unbound Unbound Bound:BGC Bound:ADP Unbound
2q2rB02 Unbound Unbound Bound:BGC Bound:ADP Unbound

Reference for Active-site residues
resource references E.C.
literature [5], [6]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1q18A01 ARG 16
1q18B01 ARG 16
1sz2A01 ARG 16
1sz2B01 ARG 16
2q2rA01 ARG 36
2q2rB01 ARG 36
1q18A02 ASP 100
1q18B02 ASP 100
1sz2A02 ASP 100
1sz2B02 ASP 100
2q2rA02 ASP 131
2q2rB02 ASP 131

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[5]
p.6925-6926
[6]
p.1222

References
[1]
Resource
Comments
Medline ID
PubMed ID 2005085
Journal J Biol Chem
Year 1991
Volume 266
Pages 5359-62
Authors Arora KK, Filburn CR, Pedersen PL
Title Glucose phosphorylation. Site-directed mutations which impair the catalytic function of hexokinase.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 10749890
Journal J Biol Chem
Year 2000
Volume 275
Pages 20814-21
Authors Kuser PR, Krauchenco S, Antunes OA, Polikarpov I
Title The high resolution crystal structure of yeast hexokinase PII with the correct primary sequence provides new insights into its mechanism of action. J Biol Chem.
Related PDB 1ig8
Related UniProtKB
[3]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH GLUCOSE; GLUCOSE-6-PHOSPHATE AND ADP.
Medline ID
PubMed ID 10686099
Journal J Mol Biol
Year 2000
Volume 296
Pages 1001-15
Authors Aleshin AE, Kirby C, Liu X, Bourenkov GP, Bartunik HD, Fromm HJ, Honzatko RB
Title Crystal structures of mutant monomeric hexokinase I reveal multiple ADP binding sites and conformational changes relevant to allosteric regulation.
Related PDB 1cza 1dgk
Related UniProtKB P19367
[4]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH AMP AND GLUCOSE, AND SUBUNIT.
Medline ID
PubMed ID 12909015
Journal J Mol Biol
Year 2003
Volume 331
Pages 871-83
Authors Ito S, Fushinobu S, Jeong JJ, Yoshioka I, Koga S, Shoun H, Wakagi T
Title Crystal structure of an ADP-dependent glucokinase from Pyrococcus furiosus: implications for a sugar-induced conformational change in ADP-dependent kinase.
Related PDB 1ua4
Related UniProtKB Q9V2Z6 Q7M537
[5]
Resource
Comments
Medline ID
PubMed ID 15466045
Journal J Bacteriol
Year 2004
Volume 186
Pages 6915-27
Authors Lunin VV, Li Y, Schrag JD, Iannuzzi P, Cygler M, Matte A
Title Crystal structures of Escherichia coli ATP-dependent glucokinase and its complex with glucose.
Related PDB 1q18 1sz2
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 17761195
Journal J Mol Biol
Year 2007
Volume 372
Pages 1215-26
Authors Cordeiro AT, Caceres AJ, Vertommen D, Concepcion JL, Michels PA, Versees W
Title The crystal structure of Trypanosoma cruzi glucokinase reveals features determining oligomerization and anomer specificity of hexose-phosphorylating enzymes.
Related PDB 2q2r
Related UniProtKB

Comments
Glucokinases (EC=2.7.1.2) are functionally distinct from hexokinases (EC=2.7.1.1) with respect to their narrow specificity for glucose as a substrate.
Although this enzyme binds magnesium ion, it is not directly bound to any residues. It seems to be bound to substrate, ATP, and water molecules (see [3],[5]). The conserved residues, Asp29 and Asp131 (of 2q2r), seems to interarct with the magnesium ion through water molecules.
According to the literature [5] and [6], this enzyme catalyzes the following reaction:
(1) Asp131 (of 2q2r) acts as a general base to deprotonate the O6 atom of substrate, glucose.
(2) The activated O6-hydroxyl group of glucose makes a nucleophilic attack on the gamma-phosphoryl group of the second substrate, ATP. This reaction proceeds by a SN2-like mechanism.
(3) The developing negative charge on the transferred group, the gamma-phosphoryl group, might be stabilized by Arg36 and the magnesium ion, during the transition state.
(4) Although no gereral acid exists as a catalytic residue, a Mg2+-coordinated water molecule might protonate the leaving beta-phosphoryl group of ADP.

Created Updated
2009-10-13 2010-02-11