EzCatDB: D00643
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DB codeD00643
RLCP classification3.103.70810.363 : Transfer
CATH domainDomain 13.30.420.40 : Nucleotidyltransferase; domain 5
Domain 23.40.367.20 : Hexokinase; domain 1Catalytic domain
E.C.2.7.1.2
CSA1q18


Enzyme Name
UniProtKBKEGG

P0A6V8Q4E4E1
Protein nameGlucokinase
Glucokinase
Glucokinase (phosphorylating)
SynonymsEC 2.7.1.2
Glucose kinase
Glucokinase 1, putative
EC 2.7.1.2
RefSeqNP_416889.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_490630.1 (Protein)
NC_007779.1 (DNA/RNA sequence)
XP_821474.1 (Protein)
XM_816381.1 (DNA/RNA sequence)
PfamPF02685 (Glucokinase)
[Graphical view]
PF02685 (Glucokinase)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00010Glycolysis / Gluconeogenesis
MAP00052Galactose metabolism
MAP00500Starch and sucrose metabolism
MAP00520Amino sugar and nucleotide sugar metabolism
MAP00521Streptomycin biosynthesis
MAP01061Biosynthesis of phenylpropanoids
MAP01062Biosynthesis of terpenoids and steroids
MAP01063Biosynthesis of alkaloids derived from shikimate pathway
MAP01064Biosynthesis of alkaloids derived from ornithine, lysine and nicotinic acid
MAP01065Biosynthesis of alkaloids derived from histidine and purine
MAP01066Biosynthesis of alkaloids derived from terpenoid and polyketide
MAP01070Biosynthesis of plant hormones

UniProtKB:Accession NumberP0A6V8Q4E4E1
Entry nameGLK_ECOLIQ4E4E1_TRYCR
ActivityATP + D-glucose = ADP + D-glucose 6-phosphate.
Subunit

Subcellular locationCytoplasm.
Cofactor


Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00305C00002C00031C00008C00092
CompoundMagnesiumATPD-glucoseADPD-glucose 6-phosphate
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotidecarbohydrateamine group,nucleotidecarbohydrate,phosphate group/phosphate ion
ChEBI18420
15422
4167
16761
4170
PubChem888
5957
5793
6022
5958
             
1q18A01UnboundUnboundUnboundUnboundUnbound
1q18B01UnboundUnboundUnboundUnboundUnbound
1sz2A01UnboundUnboundUnboundUnboundUnbound
1sz2B01UnboundUnboundUnboundUnboundUnbound
2q2rA01UnboundUnboundUnboundUnboundUnbound
2q2rB01UnboundUnboundUnboundUnboundUnbound
1q18A02UnboundUnboundUnboundUnboundUnbound
1q18B02UnboundUnboundUnboundUnboundUnbound
1sz2A02UnboundUnboundBound:BGCUnboundUnbound
1sz2B02UnboundUnboundBound:BGCUnboundUnbound
2q2rA02UnboundUnboundBound:BGCBound:ADPUnbound
2q2rB02UnboundUnboundBound:BGCBound:ADPUnbound

Active-site residues
resource
literature [5], [6]
pdbCatalytic residues
         
1q18A01ARG 16
1q18B01ARG 16
1sz2A01ARG 16
1sz2B01ARG 16
2q2rA01ARG 36
2q2rB01ARG 36
1q18A02ASP 100
1q18B02ASP 100
1sz2A02ASP 100
1sz2B02ASP 100
2q2rA02ASP 131
2q2rB02ASP 131

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[5]p.6925-6926
[6]p.1222

references
[1]
PubMed ID2005085
JournalJ Biol Chem
Year1991
Volume266
Pages5359-62
AuthorsArora KK, Filburn CR, Pedersen PL
TitleGlucose phosphorylation. Site-directed mutations which impair the catalytic function of hexokinase.
[2]
PubMed ID10749890
JournalJ Biol Chem
Year2000
Volume275
Pages20814-21
AuthorsKuser PR, Krauchenco S, Antunes OA, Polikarpov I
TitleThe 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 PDB1ig8
[3]
CommentsX-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH GLUCOSE; GLUCOSE-6-PHOSPHATE AND ADP.
PubMed ID10686099
JournalJ Mol Biol
Year2000
Volume296
Pages1001-15
AuthorsAleshin AE, Kirby C, Liu X, Bourenkov GP, Bartunik HD, Fromm HJ, Honzatko RB
TitleCrystal structures of mutant monomeric hexokinase I reveal multiple ADP binding sites and conformational changes relevant to allosteric regulation.
Related PDB1cza,1dgk
Related UniProtKBP19367
[4]
CommentsX-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH AMP AND GLUCOSE, AND SUBUNIT.
PubMed ID12909015
JournalJ Mol Biol
Year2003
Volume331
Pages871-83
AuthorsIto S, Fushinobu S, Jeong JJ, Yoshioka I, Koga S, Shoun H, Wakagi T
TitleCrystal structure of an ADP-dependent glucokinase from Pyrococcus furiosus: implications for a sugar-induced conformational change in ADP-dependent kinase.
Related PDB1ua4
Related UniProtKBQ9V2Z6,Q7M537
[5]
PubMed ID15466045
JournalJ Bacteriol
Year2004
Volume186
Pages6915-27
AuthorsLunin VV, Li Y, Schrag JD, Iannuzzi P, Cygler M, Matte A
TitleCrystal structures of Escherichia coli ATP-dependent glucokinase and its complex with glucose.
Related PDB1q18,1sz2
[6]
PubMed ID17761195
JournalJ Mol Biol
Year2007
Volume372
Pages1215-26
AuthorsCordeiro AT, Caceres AJ, Vertommen D, Concepcion JL, Michels PA, Versees W
TitleThe crystal structure of Trypanosoma cruzi glucokinase reveals features determining oligomerization and anomer specificity of hexose-phosphorylating enzymes.
Related PDB2q2r

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.

createdupdated
2009-10-132010-02-11


Copyright: Nozomi Nagano, JST & CBRC-AIST
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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 2008)
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)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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