EzCatDB: D00416

DB codeD00416
RLCP classification3.103.70000.357
CATH domainDomain 13.40.1190.20Catalytic domain
Domain 23.30.1110.10Catalytic domain
E.C.2.7.1.20
CSA1lij,1lio
MACiEM0209

CATH domainRelated DB codes (homologues)
3.40.1190.20S00534,S00541,S00678,S00705,S00903,S00904,S00905,S00453

Enzyme Name
Swiss-protKEGG

P55263Q9TVW2
Protein nameAdenosine kinaseAdenosine kinaseadenosine kinase
adenosine kinase (phosphorylating)
SynonymsAK
EC 2.7.1.20
Adenosine 5''-phosphotransferase
AK
EC 2.7.1.20
Adenosine 5''-phosphotransferase

KEGG pathways
MAP codePathways
MAP00230Purine metabolism

Swiss-prot:Accession NumberP55263Q9TVW2
Entry nameADK_HUMANADK_TOXGO
ActivityATP + adenosine = ADP + AMP.ATP + adenosine = ADP + AMP.
SubunitMonomer.
Subcellular location

CofactorBinds 3 magnesium ions per subunit.Binds 1 magnesium ion per subunit.


CofactorsSubstratesProducts
KEGG-idC00305C00002C00212C00008C00020
CompoundMagnesiumATPAdenosineADPAMP
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotideamine group,nucleotideamine group,nucleotideamine group,nucleotide
1dgmA01UnboundUnboundBound:ADNUnboundUnbound
1dgyA01Bound:_MGAnalogue:ACPBound:ADNUnboundUnbound
1dh0A01UnboundUnboundBound:ADNAnalogue:ADNUnbound
1dh1A01Bound:_MGAnalogue:ACPAnalogue:RPPUnboundUnbound
1dh2A01UnboundUnboundUnboundUnboundUnbound
1liiA01Bound:_MGAnalogue:ACPBound:ADNUnboundUnbound
1lijA01Bound:_MGAnalogue:ACPAnalogue:RPPUnboundUnbound
1likA01UnboundUnboundBound:ADNAnalogue:ADNUnbound
1lioA01UnboundUnboundUnboundUnboundUnbound
1bx4A01Bound:_MGUnboundBound:ADNAnalogue:ADNUnbound
1dgmA02UnboundUnboundUnboundUnboundUnbound
1dgyA02UnboundUnboundUnboundUnboundUnbound
1dh0A02UnboundUnboundUnboundUnboundUnbound
1dh1A02UnboundUnboundUnboundUnboundUnbound
1dh2A02UnboundUnboundUnboundUnboundUnbound
1liiA02UnboundUnboundUnboundUnboundUnbound
1lijA02UnboundUnboundUnboundUnboundUnbound
1likA02UnboundUnboundUnboundUnboundUnbound
1lioA02UnboundUnboundUnboundUnboundUnbound
1bx4A02Bound:2x_MGUnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P55263, Q9TVW2 & literature [2], [10]
pdbCatalytic residuesCofactor-binding residuesMain-chain involved in catalysis
1dgmA01ASP 318
THR 313(magnesium binding)
GLY 315;GLY 317
1dgyA01ASP 318
THR 313(magnesium binding)
GLY 315;GLY 317
1dh0A01ASP 318
THR 313(magnesium binding)
GLY 315;GLY 317
1dh1A01ASP 318
THR 313(magnesium binding)
GLY 315;GLY 317
1dh2A01ASP 318
THR 313(magnesium binding)
GLY 315;GLY 317
1liiA01ASP 318
THR 313(magnesium binding)
GLY 315;GLY 317
1lijA01ASP 318
THR 313(magnesium binding)
GLY 315;GLY 317
1likA01ASP 318
THR 313(magnesium binding)
GLY 315;GLY 317
1lioA01ASP 318
THR 313(magnesium binding)
GLY 315;GLY 317
1bx4A01ASP 300
THR 295(magnesium binding)
GLY 297;GLY 299
1dgmA02ARG 136


1dgyA02ARG 136


1dh0A02ARG 136


1dh1A02ARG 136


1dh2A02ARG 136


1liiA02ARG 136


1lijA02ARG 136


1likA02ARG 136


1lioA02ARG 136


1bx4A02ARG 132



References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]Fig.12, p.15617-156182
[5]Fig.6, p.3923
[10]p.886-890, Fig.6

references
[1]
PubMed ID2538441
JournalJ Biol Chem
Year1989
Volume264
Pages4356-61
AuthorsBhaumik D, Datta AK
TitleImmunochemical and catalytic characteristics of adenosine kinase from Leishmania donovani.
[2]
CommentsX-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF SHORT ISOFORM
Medline ID99060037
PubMed ID9843365
JournalBiochemistry
Year1998
Volume37
Pages15607-20
AuthorsMathews II, Erion MD, Ealick SE
TitleStructure of human adenosine kinase at 1.5 A resolution.
Related PDB1bx4
Related Swiss-protP55263
[3]
PubMed ID10518797
JournalEur J Biochem
Year1999
Volume265
Pages1015-21
AuthorsCarret C, Delbecq S, Labesse G, Carcy B, Precigout E, Moubri K, Schetters TP, Gorenflot A
TitleCharacterization and molecular cloning of an adenosine kinase from Babesia canis rossi.
[4]
PubMed ID10666633
JournalActa Crystallogr D Biol Crystallogr
Year2000
Volume56
Pages76-8
AuthorsRecacha R, Talalaev A, DeLucas LJ, Chattopadhyay D
TitleToxoplasma gondii adenosine kinase: expression, purification, characterization, crystallization and preliminary crystallographic analysis.
[5]
PubMed ID10964675
JournalBiochem Biophys Res Commun
Year2000
Volume275
Pages386-93
AuthorsMaj MC, Singh B, Gupta RS
TitleStructure-activity studies on mammalian adenosine kinase.
[6]
PubMed ID11123986
JournalJ Med Chem
Year2000
Volume43
Pages4781-6
AuthorsHajduk PJ, Gomtsyan A, Didomenico S, Cowart M, Bayburt EK, Solomon L, Severin J, Smith R, Walter K, Holzman TF, Stewart A, McGaraughty S, Jarvis MF, Kowaluk EA, Fesik SW
TitleDesign of adenosine kinase inhibitors from the NMR-based screening of fragments.
[7]
PubMed ID10956197
JournalJ Med Chem
Year2000
Volume43
Pages2894-905
AuthorsUgarkar BG, Castellino AJ, DaRe JM, Kopcho JJ, Wiesner JB, Schanzer JM, Erion MD
TitleAdenosine kinase inhibitors. 2. Synthesis, enzyme inhibition, and antiseizure activity of diaryltubercidin analogues.
[8]
CommentsX-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS)
Medline ID20135988
PubMed ID10669608
JournalJ Mol Biol
Year2000
Volume296
Pages549-67
AuthorsSchumacher MA, Scott DM, Mathews II, Ealick SE, Roos DS, Ullman B, Brennan RG
TitleCrystal structures of Toxoplasma gondii adenosine kinase reveal a novel catalytic mechanism and prodrug binding.
Related PDB1dgy,1dh0,1dh2
Related Swiss-protQ9TVM2
[9]
CommentsX-ray crystallography
PubMed ID10794412
JournalProtein Sci
Year2000
Volume9
Pages704-12
AuthorsCook WJ, DeLucas LJ, Chattopadhyay D
TitleCrystal structure of adenosine kinase from Toxoplasma gondii at 1.8 A resolution.
Related PDB1dgm,1dh1
[10]
PubMed ID10801355
JournalJ Mol Biol
Year2000
Volume298
Pages875-93
AuthorsSchumacher MA, Scott DM, Mathews II, Ealick SE, Roos DS, Ullman B, Brennan RG
TitleCrystal structures of Toxoplasma gondii adenosine kinase reveal a novel catalytic mechanism and prodrug binding.
Related PDB1lii,1lij,1lik,1lio
[11]
PubMed ID11286887
JournalStructure (Camb)
Year2001
Volume9
Pages205-14
AuthorsIto S, Fushinobu S, Yoshioka I, Koga S, Matsuzawa H, Wakagi T
TitleStructural basis for the ADP-specificity of a novel glucokinase from a hyperthermophilic archaeon.
[12]
PubMed ID12244046
JournalJ Biol Chem
Year2002
Volume277
Pages47451-60
AuthorsChakraborty A, Das I, Datta R, Sen B, Bhattacharyya D, Mandal C, Datta AK
TitleA single-domain cyclophilin from Leishmania donovani reactivates soluble aggregates of adenosine kinase by isomerase-independent chaperone function.
[13]
PubMed ID12166937
JournalJ Med Chem
Year2002
Volume45
Pages3639-48
AuthorsGomtsyan A, Didomenico S, Lee CH, Matulenko MA, Kim K, Kowaluk EA, Wismer CT, Mikusa J, Yu H, Kohlhaas K, Jarvis MF, Bhagwat SS
TitleDesign, synthesis, and structure-activity relationship of 6-alkynylpyrimidines as potent adenosine kinase inhibitors.

comments
According to the literature [2], [5], & [10], the catalytic reaction of this enzyme proceeds via SN2-mechanism, in which acceptor 5'-hydroxyl group activated by a general base makes a nucleophilic attack on gamma-phosphate of ATP. Here, Asp318 (PDB;1dgy) acts as the general base. Moreover, Arg136 (PDB;1dgy) stabilizes the negatively charged gamma-phosphate group during transition state, together with an anion hole composed of mainchain amide of Gly315 and Gly317. These positive charged elements will increase the electrophilicity of the gamma-phosphate.
Furthermore, magnesium ion plays an important role in the catalysis. However, whilst the ion is bridging beta- and gamma-phosphate groups of ATP in the enzyme from human, the magnesium ion interacts with alpha- and beta-phosphate groups in the enzyme from T. gondii. In either case, the magnesium ion would neutralize the negatively charged phosphate groups to facilitate the catalysis (see [10]).

createdupdated
2003-07-222009-02-26


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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