D00416
type: Enzyme
rlcp: p357
cath: UDP-N-acetylmuramoyl-L-alanine
cath: Adenosine kinase, small domain
ec: https://purl.uniprot.org/enzyme/2.7.1.20
csa: 1lij
csa: 1lio
macie: M0209
uniprot: P55263
uniprot: Q9TVW2
kegg enzyme: adenosine kinase
kegg enzyme: adenosine kinase (phosphorylating)
kegg pathway: Purine metabolism
kegg cofactor: Magnesium
kegg substrate: ATP
kegg substrate: Adenosine
kegg product: ADP
kegg product: AMP
pdb: 1dgmA01
pdb: 1dgyA01
pdb: 1dh0A01
pdb: 1dh1A01
pdb: 1dh2A01
pdb: 1liiA01
pdb: 1lijA01
pdb: 1likA01
pdb: 1lioA01
pdb: 1bx4A01
pdb: 1dgmA02
pdb: 1dgyA02
pdb: 1dh0A02
pdb: 1dh1A02
pdb: 1dh2A02
pdb: 1liiA02
pdb: 1lijA02
pdb: 1likA02
pdb: 1lioA02
pdb: 1bx4A02
pdb bound state: Unbound
  compound: ATP
  pdb: 1dgmA01
pdb bound state: Analogue
  compound: ATP
  pdb: 1dgyA01
  ligand het code: ACP
pdb bound state: Unbound
  compound: ATP
  pdb: 1dh0A01
pdb bound state: Analogue
  compound: ATP
  pdb: 1dh1A01
  ligand het code: ACP
pdb bound state: Unbound
  compound: ATP
  pdb: 1dh2A01
pdb bound state: Analogue
  compound: ATP
  pdb: 1liiA01
  ligand het code: ACP
pdb bound state: Analogue
  compound: ATP
  pdb: 1lijA01
  ligand het code: ACP
pdb bound state: Unbound
  compound: ATP
  pdb: 1likA01
pdb bound state: Unbound
  compound: ATP
  pdb: 1lioA01
pdb bound state: Unbound
  compound: ATP
  pdb: 1bx4A01
pdb bound state: Unbound
  compound: ATP
  pdb: 1dgmA02
pdb bound state: Unbound
  compound: ATP
  pdb: 1dgyA02
pdb bound state: Unbound
  compound: ATP
  pdb: 1dh0A02
pdb bound state: Unbound
  compound: ATP
  pdb: 1dh1A02
pdb bound state: Unbound
  compound: ATP
  pdb: 1dh2A02
pdb bound state: Unbound
  compound: ATP
  pdb: 1liiA02
pdb bound state: Unbound
  compound: ATP
  pdb: 1lijA02
pdb bound state: Unbound
  compound: ATP
  pdb: 1likA02
pdb bound state: Unbound
  compound: ATP
  pdb: 1lioA02
pdb bound state: Unbound
  compound: ATP
  pdb: 1bx4A02
pdb bound state: Analogue
  compound: Adenosine
  pdb: 1dh1A01
  ligand het code: RPP
pdb bound state: Unbound
  compound: Adenosine
  pdb: 1dh2A01
pdb bound state: Analogue
  compound: Adenosine
  pdb: 1lijA01
  ligand het code: RPP
pdb bound state: Unbound
  compound: Adenosine
  pdb: 1lioA01
active site residues resources: Characterization and molecular cloning of an adenosine kinase from Babesia canis rossi.
active site residues resources: Structural basis for the ADP-specificity of a novel glucokinase from a hyperthermophilic archaeon.
active site residues resources: P55263
active site residues resources: Q9TVW2
references: Immunochemical and catalytic characteristics of adenosine kinase from Leishmania donovani.
references: Structure of human adenosine kinase at 1.5 A resolution.
references: Characterization and molecular cloning of an adenosine kinase from Babesia canis rossi.
references: Toxoplasma gondii adenosine kinase: expression, purification, characterization, crystallization and preliminary crystallographic analysis.
references: Structure-activity studies on mammalian adenosine kinase.
references: Design of adenosine kinase inhibitors from the NMR-based screening of fragments.
references: Adenosine kinase inhibitors. 2. Synthesis, enzyme inhibition, and antiseizure activity of diaryltubercidin analogues.
references: Crystal structures of Toxoplasma gondii adenosine kinase reveal a novel catalytic mechanism and prodrug binding.
references: Crystal structure of adenosine kinase from Toxoplasma gondii at 1.8 A resolution.
references: Structural basis for the ADP-specificity of a novel glucokinase from a hyperthermophilic archaeon.
references: A single-domain cyclophilin from Leishmania donovani reactivates soluble aggregates of adenosine kinase by isomerase-independent chaperone function.
references: Design, synthesis, and structure-activity relationship of 6-alkynylpyrimidines as potent adenosine kinase inhibitors.
comment: 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]).

UDP-N-acetylmuramoyl-L-alanine
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.40.1190.20
catalytic domain: index.html

Adenosine kinase, small domain
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.30.1110.10
catalytic domain: index.html

Purine metabolism
type: KeggPathway
references: KEGG:MAP00230

Magnesium
type: KeggCofactor
references: KEGG:C00305
compound type: divalent metal (Ca2+, Mg2+)
references: CHEBI:18420
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

ATP
type: KeggSubstrate
references: KEGG:C00002
compound type: amine group
compound type: nucleotide
references: CHEBI:15422
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

Adenosine
type: KeggSubstrate
references: KEGG:C00212
compound type: amine group
compound type: nucleotide
references: CHEBI:16335
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

ADP
type: KeggProduct
references: KEGG:C00008
compound type: amine group
compound type: nucleotide
references: CHEBI:16761
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

AMP
type: KeggProduct
references: KEGG:C00020
compound type: amine group
compound type: nucleotide
references: CHEBI:16027
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

1dgmA01
type: Pdb
references: 1dgm
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1dgm
catalytic residue: ASP 318
cofactor binding residue: THR 313(magnesium binding)
main chain in catalysis: GLY 315;GLY 317

1dgyA01
type: Pdb
references: 1dgy
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1dgy
catalytic residue: ASP 318
cofactor binding residue: THR 313(magnesium binding)
main chain in catalysis: GLY 315;GLY 317

1dh0A01
type: Pdb
references: 1dh0
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1dh0
catalytic residue: ASP 318
cofactor binding residue: THR 313(magnesium binding)
main chain in catalysis: GLY 315;GLY 317

1dh1A01
type: Pdb
references: 1dh1
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1dh1
catalytic residue: ASP 318
cofactor binding residue: THR 313(magnesium binding)
main chain in catalysis: GLY 315;GLY 317

1dh2A01
type: Pdb
references: 1dh2
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1dh2
catalytic residue: ASP 318
cofactor binding residue: THR 313(magnesium binding)
main chain in catalysis: GLY 315;GLY 317

1liiA01
type: Pdb
references: 1lii
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1lii
catalytic residue: ASP 318
cofactor binding residue: THR 313(magnesium binding)
main chain in catalysis: GLY 315;GLY 317

1lijA01
type: Pdb
references: 1lij
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1lij
catalytic residue: ASP 318
cofactor binding residue: THR 313(magnesium binding)
main chain in catalysis: GLY 315;GLY 317

1likA01
type: Pdb
references: 1lik
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1lik
catalytic residue: ASP 318
cofactor binding residue: THR 313(magnesium binding)
main chain in catalysis: GLY 315;GLY 317

1lioA01
type: Pdb
references: 1lio
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1lio
catalytic residue: ASP 318
cofactor binding residue: THR 313(magnesium binding)
main chain in catalysis: GLY 315;GLY 317

1bx4A01
type: Pdb
references: 1bx4
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1bx4
catalytic residue: ASP 300
cofactor binding residue: THR 295(magnesium binding)
main chain in catalysis: GLY 297;GLY 299

1dgmA02
type: Pdb
references: 1dgm
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1dgm
catalytic residue: ARG 136

1dgyA02
type: Pdb
references: 1dgy
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1dgy
catalytic residue: ARG 136

1dh0A02
type: Pdb
references: 1dh0
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1dh0
catalytic residue: ARG 136

1dh1A02
type: Pdb
references: 1dh1
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1dh1
catalytic residue: ARG 136

1dh2A02
type: Pdb
references: 1dh2
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1dh2
catalytic residue: ARG 136

1liiA02
type: Pdb
references: 1lii
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1lii
catalytic residue: ARG 136

1lijA02
type: Pdb
references: 1lij
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1lij
catalytic residue: ARG 136

1likA02
type: Pdb
references: 1lik
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1lik
catalytic residue: ARG 136

1lioA02
type: Pdb
references: 1lio
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1lio
catalytic residue: ARG 136

1bx4A02
type: Pdb
references: 1bx4
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1bx4
catalytic residue: ARG 132

Immunochemical and catalytic characteristics of adenosine kinase from Leishmania donovani.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/2538441
journal: J Biol Chem
volume: 264
pages: 4356-61
published year: 1989
authors:
  item: Bhaumik D
  item: Datta AK

Structure of human adenosine kinase at 1.5 A resolution.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF SHORT ISOFORM
medline id: 99060037
references: http://www.ncbi.nlm.nih.gov/pubmed/9843365
journal: Biochemistry
volume: 37
pages: 15607-20
published year: 1998
authors:
  item: Mathews II
  item: Erion MD
  item: Ealick SE
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P55263

Characterization and molecular cloning of an adenosine kinase from Babesia canis rossi.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10518797
journal: Eur J Biochem
volume: 265
pages: 1015-21
published year: 1999
authors:
  item: Carret C
  item: Delbecq S
  item: Labesse G
  item: Carcy B
  item: Precigout E
  item: Moubri K
  item: Schetters TP
  item: Gorenflot A

Toxoplasma gondii adenosine kinase: expression, purification, characterization, crystallization and preliminary crystallographic analysis.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10666633
journal: Acta Crystallogr D Biol Crystallogr
volume: 56
pages: 76-8
published year: 2000
authors:
  item: Recacha R
  item: Talalaev A
  item: DeLucas LJ
  item: Chattopadhyay D

Structure-activity studies on mammalian adenosine kinase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10964675
journal: Biochem Biophys Res Commun
volume: 275
pages: 386-93
published year: 2000
authors:
  item: Maj MC
  item: Singh B
  item: Gupta RS

Design of adenosine kinase inhibitors from the NMR-based screening of fragments.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11123986
journal: J Med Chem
volume: 43
pages: 4781-6
published year: 2000
authors:
  item: Hajduk PJ
  item: Gomtsyan A
  item: Didomenico S
  item: Cowart M
  item: Bayburt EK
  item: Solomon L
  item: Severin J
  item: Smith R
  item: Walter K
  item: Holzman TF
  item: Stewart A
  item: McGaraughty S
  item: Jarvis MF
  item: Kowaluk EA
  item: Fesik SW

Adenosine kinase inhibitors. 2. Synthesis, enzyme inhibition, and antiseizure activity of diaryltubercidin analogues.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10956197
journal: J Med Chem
volume: 43
pages: 2894-905
published year: 2000
authors:
  item: Ugarkar BG
  item: Castellino AJ
  item: DaRe JM
  item: Kopcho JJ
  item: Wiesner JB
  item: Schanzer JM
  item: Erion MD

Crystal structures of Toxoplasma gondii adenosine kinase reveal a novel catalytic mechanism and prodrug binding.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS)
medline id: 20135988
references: http://www.ncbi.nlm.nih.gov/pubmed/10669608
journal: J Mol Biol
volume: 296
pages: 549-67
published year: 2000
authors:
  item: Schumacher MA
  item: Scott DM
  item: Mathews II
  item: Ealick SE
  item: Roos DS
  item: Ullman B
  item: Brennan RG
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: Q9TVM2

Crystal structure of adenosine kinase from Toxoplasma gondii at 1.8 A resolution.
type: BibliographicResource
comment: X-ray crystallography
references: http://www.ncbi.nlm.nih.gov/pubmed/10794412
journal: Protein Sci
volume: 9
pages: 704-12
published year: 2000
authors:
  item: Cook WJ
  item: DeLucas LJ
  item: Chattopadhyay D
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Crystal structures of Toxoplasma gondii adenosine kinase reveal a novel catalytic mechanism and prodrug binding.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10801355
journal: J Mol Biol
volume: 298
pages: 875-93
published year: 2000
authors:
  item: Schumacher MA
  item: Scott DM
  item: Mathews II
  item: Ealick SE
  item: Roos DS
  item: Ullman B
  item: Brennan RG
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Structural basis for the ADP-specificity of a novel glucokinase from a hyperthermophilic archaeon.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11286887
journal: Structure (Camb)
volume: 9
pages: 205-14
published year: 2001
authors:
  item: Ito S
  item: Fushinobu S
  item: Yoshioka I
  item: Koga S
  item: Matsuzawa H
  item: Wakagi T

A single-domain cyclophilin from Leishmania donovani reactivates soluble aggregates of adenosine kinase by isomerase-independent chaperone function.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12244046
journal: J Biol Chem
volume: 277
pages: 47451-60
published year: 2002
authors:
  item: Chakraborty A
  item: Das I
  item: Datta R
  item: Sen B
  item: Bhattacharyya D
  item: Mandal C
  item: Datta AK

Design, synthesis, and structure-activity relationship of 6-alkynylpyrimidines as potent adenosine kinase inhibitors.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12166937
journal: J Med Chem
volume: 45
pages: 3639-48
published year: 2002
authors:
  item: Gomtsyan A
  item: Didomenico S
  item: Lee CH
  item: Matulenko MA
  item: Kim K
  item: Kowaluk EA
  item: Wismer CT
  item: Mikusa J
  item: Yu H
  item: Kohlhaas K
  item: Jarvis MF
  item: Bhagwat SS

Analogue
compound: ADP
pdb: 1dh0A01
ligand het code: ADN

Analogue
compound: ADP
pdb: 1likA01
ligand het code: ADN

Analogue
compound: ADP
pdb: 1bx4A01
ligand het code: ADN

ReferenceForCatalyticMechanism
reference index: 2
reference section: Fig.12, p.15617-15618
reference step: 2

ReferenceForCatalyticMechanism
reference index: 5
reference section: Fig.6, p.392
reference step: 3

ReferenceForCatalyticMechanism
reference index: 10
reference section: p.886-890, Fig.6