DB code: D00416

RLCP classification 3.103.70000.357 : Transfer
CATH domain 3.40.1190.20 : UDP-N-acetylmuramoyl-L-alanine Catalytic domain
3.30.1110.10 : Adenosine kinase, small domain Catalytic domain
E.C. 2.7.1.20
CSA 1lio 1lij
M-CSA 1lio 1lij
MACiE M0209

CATH domain Related DB codes (homologues)
3.40.1190.20 : UDP-N-acetylmuramoyl-L-alanine S00534 S00541 S00678 S00705 S00903 S00904 S00905 S00453

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P55263 Adenosine kinase
AK
EC 2.7.1.20
Adenosine 5''-phosphotransferase
NP_001114.2 (Protein)
NM_001123.3 (DNA/RNA sequence)
NP_001189378.1 (Protein)
NM_001202449.1 (DNA/RNA sequence)
NP_001189379.1 (Protein)
NM_001202450.1 (DNA/RNA sequence)
NP_006712.2 (Protein)
NM_006721.3 (DNA/RNA sequence)
PF00294 (PfkB)
[Graphical View]
Q9TVW2 Adenosine kinase
AK
EC 2.7.1.20
Adenosine 5''-phosphotransferase
PF00294 (PfkB)
[Graphical View]

KEGG enzyme name
adenosine kinase
adenosine kinase (phosphorylating)

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q9TVW2 ADK_TOXGO ATP + adenosine = ADP + AMP. Binds 1 magnesium ion per subunit.
P55263 ADK_HUMAN ATP + adenosine = ADP + AMP. Monomer. Binds 3 magnesium ions per subunit.

KEGG Pathways
Map code Pathways E.C.
MAP00230 Purine metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00002 C00212 C00008 C00020
E.C.
Compound Magnesium ATP Adenosine ADP AMP
Type divalent metal (Ca2+, Mg2+) amine group,nucleotide amine group,nucleotide amine group,nucleotide amine group,nucleotide
ChEBI 18420
15422
16335
16761
16027
PubChem 888
5957
60961
6022
6083
1dgmA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:ADN Unbound Unbound
1dgyA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Analogue:ACP Bound:ADN Unbound Unbound
1dh0A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:ADN Analogue:ADN Unbound
1dh1A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Analogue:ACP Analogue:RPP Unbound Unbound
1dh2A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1liiA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Analogue:ACP Bound:ADN Unbound Unbound
1lijA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Analogue:ACP Analogue:RPP Unbound Unbound
1likA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:ADN Analogue:ADN Unbound
1lioA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1bx4A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Unbound Bound:ADN Analogue:ADN Unbound
1dgmA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1dgyA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1dh0A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1dh1A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1dh2A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1liiA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1lijA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1likA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1lioA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1bx4A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_MG Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P55263, Q9TVW2 & literature [2], [10]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1dgmA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 318 THR 313(magnesium binding) GLY 315;GLY 317
1dgyA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 318 THR 313(magnesium binding) GLY 315;GLY 317
1dh0A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 318 THR 313(magnesium binding) GLY 315;GLY 317
1dh1A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 318 THR 313(magnesium binding) GLY 315;GLY 317
1dh2A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 318 THR 313(magnesium binding) GLY 315;GLY 317
1liiA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 318 THR 313(magnesium binding) GLY 315;GLY 317
1lijA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 318 THR 313(magnesium binding) GLY 315;GLY 317
1likA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 318 THR 313(magnesium binding) GLY 315;GLY 317
1lioA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 318 THR 313(magnesium binding) GLY 315;GLY 317
1bx4A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 300 THR 295(magnesium binding) GLY 297;GLY 299
1dgmA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 136
1dgyA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 136
1dh0A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 136
1dh1A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 136
1dh2A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 136
1liiA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 136
1lijA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 136
1likA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 136
1lioA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 136
1bx4A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 132

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
Fig.12, p.15617-15618 2
[5]
Fig.6, p.392 3
[10]
p.886-890, Fig.6

References
[1]
Resource
Comments
Medline ID
PubMed ID 2538441
Journal J Biol Chem
Year 1989
Volume 264
Pages 4356-61
Authors Bhaumik D, Datta AK
Title Immunochemical and catalytic characteristics of adenosine kinase from Leishmania donovani.
Related PDB
Related UniProtKB
[2]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF SHORT ISOFORM
Medline ID 99060037
PubMed ID 9843365
Journal Biochemistry
Year 1998
Volume 37
Pages 15607-20
Authors Mathews II, Erion MD, Ealick SE
Title Structure of human adenosine kinase at 1.5 A resolution.
Related PDB 1bx4
Related UniProtKB P55263
[3]
Resource
Comments
Medline ID
PubMed ID 10518797
Journal Eur J Biochem
Year 1999
Volume 265
Pages 1015-21
Authors Carret C, Delbecq S, Labesse G, Carcy B, Precigout E, Moubri K, Schetters TP, Gorenflot A
Title Characterization and molecular cloning of an adenosine kinase from Babesia canis rossi.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 10666633
Journal Acta Crystallogr D Biol Crystallogr
Year 2000
Volume 56
Pages 76-8
Authors Recacha R, Talalaev A, DeLucas LJ, Chattopadhyay D
Title Toxoplasma gondii adenosine kinase: expression, purification, characterization, crystallization and preliminary crystallographic analysis.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 10964675
Journal Biochem Biophys Res Commun
Year 2000
Volume 275
Pages 386-93
Authors Maj MC, Singh B, Gupta RS
Title Structure-activity studies on mammalian adenosine kinase.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 11123986
Journal J Med Chem
Year 2000
Volume 43
Pages 4781-6
Authors Hajduk 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
Title Design of adenosine kinase inhibitors from the NMR-based screening of fragments.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 10956197
Journal J Med Chem
Year 2000
Volume 43
Pages 2894-905
Authors Ugarkar BG, Castellino AJ, DaRe JM, Kopcho JJ, Wiesner JB, Schanzer JM, Erion MD
Title Adenosine kinase inhibitors. 2. Synthesis, enzyme inhibition, and antiseizure activity of diaryltubercidin analogues.
Related PDB
Related UniProtKB
[8]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS)
Medline ID 20135988
PubMed ID 10669608
Journal J Mol Biol
Year 2000
Volume 296
Pages 549-67
Authors Schumacher MA, Scott DM, Mathews II, Ealick SE, Roos DS, Ullman B, Brennan RG
Title Crystal structures of Toxoplasma gondii adenosine kinase reveal a novel catalytic mechanism and prodrug binding.
Related PDB 1dgy 1dh0 1dh2
Related UniProtKB Q9TVM2
[9]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10794412
Journal Protein Sci
Year 2000
Volume 9
Pages 704-12
Authors Cook WJ, DeLucas LJ, Chattopadhyay D
Title Crystal structure of adenosine kinase from Toxoplasma gondii at 1.8 A resolution.
Related PDB 1dgm 1dh1
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 10801355
Journal J Mol Biol
Year 2000
Volume 298
Pages 875-93
Authors Schumacher MA, Scott DM, Mathews II, Ealick SE, Roos DS, Ullman B, Brennan RG
Title Crystal structures of Toxoplasma gondii adenosine kinase reveal a novel catalytic mechanism and prodrug binding.
Related PDB 1lii 1lij 1lik 1lio
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 11286887
Journal Structure (Camb)
Year 2001
Volume 9
Pages 205-14
Authors Ito S, Fushinobu S, Yoshioka I, Koga S, Matsuzawa H, Wakagi T
Title Structural basis for the ADP-specificity of a novel glucokinase from a hyperthermophilic archaeon.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 12244046
Journal J Biol Chem
Year 2002
Volume 277
Pages 47451-60
Authors Chakraborty A, Das I, Datta R, Sen B, Bhattacharyya D, Mandal C, Datta AK
Title A single-domain cyclophilin from Leishmania donovani reactivates soluble aggregates of adenosine kinase by isomerase-independent chaperone function.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 12166937
Journal J Med Chem
Year 2002
Volume 45
Pages 3639-48
Authors Gomtsyan A, Didomenico S, Lee CH, Matulenko MA, Kim K, Kowaluk EA, Wismer CT, Mikusa J, Yu H, Kohlhaas K, Jarvis MF, Bhagwat SS
Title Design, synthesis, and structure-activity relationship of 6-alkynylpyrimidines as potent adenosine kinase inhibitors.
Related PDB
Related UniProtKB

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]).

Created Updated
2003-07-22 2009-02-26