EzCatDB: S00305

DB codeS00305
RLCP classification3.133.90010.394
CATH domainDomain 13.40.50.300Catalytic domain
E.C.2.7.4.3

CATH domainRelated DB codes (homologues)
3.40.50.300S00527,S00547,S00548,S00550,S00554,S00555,S00671,S00672,S00676,S00680,S00682,S00913,S00914,S00301,S00302,S00303,S00304,S00307,S00308,S00306,S00309,S00310,S00311,M00114,M00199,D00129,D00130,D00540,M00186

Enzyme Name
Swiss-protKEGG

P69441P07170P00571P08166
Protein nameAdenylate kinaseAdenylate kinase 1Adenylate kinase isoenzyme 1Adenylate kinase 2, mitochondrialadenylate kinase
myokinase
5'-AMP-kinase
adenylic kinase
adenylokinase
SynonymsAK
EC 2.7.4.3
ATP-AMP transphosphorylase
AK 1
EC 2.7.4.3
ATP-AMP transphosphorylase 1
Adenylate kinase cytosolic and mitochondrial
AK 1
EC 2.7.4.3
ATP-AMP transphosphorylase 1
Myokinase
AK 2
EC 2.7.4.3
ATP-AMP transphosphorylase 2

KEGG pathways
MAP codePathways
MAP00230Purine metabolism

Swiss-prot:Accession NumberP69441P07170P00571P08166
Entry nameKAD_ECOLIKAD1_YEASTKAD1_PIGKAD2_BOVIN
ActivityATP + AMP = 2 ADP.ATP + AMP = 2 ADP.ATP + AMP = 2 ADP.ATP + AMP = 2 ADP.
SubunitMonomer.Monomer.Monomer.Monomer.
Subcellular locationCytoplasm.Cytoplasm.Cytoplasm.Mitochondrion intermembrane space.
Cofactor





CofactorsSubstratesProducts
KEGG-idC00305C00002C00020C00008C00008
CompoundMagnesiumATPAMPADP (from ATP)ADP (from AMP)
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotideamine group,nucleotideamine group,nucleotideamine group,nucleotide
1akeAUnboundAnalogue:AP5(ATP)Analogue:AP5(AMP)UnboundUnbound
1akeBUnboundAnalogue:AP5(ATP)Analogue:AP5(AMP)UnboundUnbound
1ankAUnboundAnalogue:ANPBound:AMPUnboundUnbound
1ankBUnboundAnalogue:ANPBound:AMPUnboundUnbound
1e4vAUnboundAnalogue:AP5(ATP)Analogue:AP5(AMP)UnboundUnbound
1e4vBUnboundAnalogue:AP5(ATP)Analogue:AP5(AMP)UnboundUnbound
1e4yAUnboundAnalogue:AP5(ATP)Analogue:AP5(AMP)UnboundUnbound
1e4yBUnboundAnalogue:AP5(ATP)Analogue:AP5(AMP)UnboundUnbound
1eckAUnboundUnboundBound:AMPBound:ADPUnbound
1eckBUnboundUnboundBound:AMPBound:ADPUnbound
2eckAUnboundUnboundBound:AMPBound:ADPUnbound
2eckBUnboundUnboundBound:AMPBound:ADPUnbound
3hpqAUnboundAnalogue:AP5(ATP)Analogue:AP5(AMP)UnboundUnbound
3hpqBUnboundAnalogue:AP5(ATP)Analogue:AP5(AMP)UnboundUnbound
3hprAUnboundAnalogue:AP5(ATP)Analogue:AP5(AMP)UnboundUnbound
3hprBUnboundAnalogue:AP5(ATP)Analogue:AP5(AMP)UnboundUnbound
4akeAUnboundUnboundUnboundUnboundUnbound
4akeBUnboundUnboundUnboundUnboundUnbound
1akyAUnboundAnalogue:AP5(ATP)Analogue:AP5(AMP)UnboundUnbound
1dvrAUnboundAnalogue:ATFUnboundUnboundUnbound
1dvrBUnboundAnalogue:ATFUnboundUnboundUnbound
2akyABound:_MGAnalogue:AP5(ATP)Analogue:AP5(AMP)UnboundUnbound
3akyAUnboundAnalogue:AP5(ATP)Analogue:AP5(AMP)UnboundUnbound
1ak2AUnboundUnboundUnboundUnboundUnbound
2ak2AUnboundUnboundUnboundUnboundUnbound
3adkAUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
literature [17], [18] & [19]
pdbCatalytic residuesCofactor-binding residuescomment
1akeALYS 13;ARG 36;ARG  88;ARG 156;ARG 167
ASP  84(magnesium binding)

1akeBLYS 13;ARG 36;ARG  88;ARG 156;ARG 167
ASP  84(magnesium binding)

1ankALYS 13;ARG 36;ARG  88;ARG 156;ARG 167
ASP  84(magnesium binding)

1ankBLYS 13;ARG 36;ARG  88;ARG 156;ARG 167
ASP  84(magnesium binding)

1e4vALYS 13;ARG 36;ARG  88;ARG 156;ARG 167
ASP  84(magnesium binding)

1e4vBLYS 13;ARG 36;ARG  88;ARG 156;ARG 167
ASP  84(magnesium binding)

1e4yALYS 13;ARG 36;ARG  88;ARG 156;ARG 167
ASP  84(magnesium binding)

1e4yBLYS 13;ARG 36;ARG  88;ARG 156;ARG 167
ASP  84(magnesium binding)

1eckALYS 13;ARG 36;ARG  88;ARG 156;ARG 167
ASP  84(magnesium binding)

1eckBLYS 13;ARG 36;ARG  88;ARG 156;ARG 167
ASP  84(magnesium binding)

2eckALYS 13;ARG 36;ARG  88;ARG 156;ARG 167
ASP  84(magnesium binding)

2eckBLYS 13;ARG 36;ARG  88;ARG 156;ARG 167
ASP  84(magnesium binding)

3hpqALYS 13;ARG 36;ARG  88;ARG 156;ARG 167
ASP  84(magnesium binding)

3hpqBLYS 13;ARG 36;ARG  88;ARG 156;ARG 167
ASP  84(magnesium binding)

3hprALYS 13;ARG 36;ARG  88;ARG 156;ARG 167
ASP  84(magnesium binding)
mutant V148G
3hprBLYS 13;ARG 36;ARG  88;ARG 156;ARG 167
ASP  84(magnesium binding)
mutant V148G
4akeALYS 13;ARG 36;ARG  88;ARG 156;ARG 167
ASP  84(magnesium binding)

4akeBLYS 13;ARG 36;ARG  88;ARG 156;ARG 167
ASP  84(magnesium binding)

1akyALYS 17;ARG 40;ARG  93;ARG 165;ARG 176
ASP  89(magnesium binding)

1dvrALYS 17;ARG 40;ARG  93;       ;ARG 176
                          
mutant D89V, R165I
1dvrBLYS 17;ARG 40;ARG  93;       ;ARG 176
                          
mutant D89V, R165I
2akyALYS 17;ARG 40;ARG  93;ARG 165;ARG 176
ASP  89(magnesium binding)

3akyALYS 17;ARG 40;ARG  93;ARG 165;ARG 176
ASP  89(magnesium binding)

1ak2ALYS 29;ARG 52;ARG 104;ARG 176;ARG 187
ASP 100(magnesium binding)

2ak2ALYS 29;ARG 52;ARG 104;ARG 176;ARG 187
ASP 100(magnesium binding)

3adkALYS 21;ARG 44;ARG  97;ARG 138;ARG 149
ASP  93(magnesium binding)


References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[9]p.368-370
[13]Fig.5
[17]p.5545
[18]p.6810-6813
[19]p.172-175
[20]p.3181
[26]p.1266-1269
[32]p.172-174

references
[1]
PubMed ID4367210
JournalNature
Year1974
Volume250
Pages120-3
AuthorsSchulz GE, Elzinga M, Marx F, Schrimer RH
TitleThree dimensional structure of adenyl kinase.
Related PDBP00571
[2]
PubMed ID6086335
JournalEur J Biochem
Year1984
Volume141
Pages629-36
AuthorsFrank R, Trosin M, Tomasselli AG, Schulz GE, Schirmer RH
TitleMitochondrial adenylate kinase (AK2) from bovine heart. Homology with the cytosolic isoenzyme in the catalytic region.
[3]
PubMed ID3002789
JournalEur J Biochem
Year1986
Volume154
Pages205-11
AuthorsFrank R, Trosin M, Tomasselli AG, Noda L, Krauth-Siegel RL, Schirmer RH
TitleMitochondrial adenylate kinase (AK2) from bovine heart. The complete primary structure.
[4]
PubMed ID2869483
JournalProc Natl Acad Sci U S A
Year1986
Volume83
Pages907-11
AuthorsFry DC, Kuby SA, Mildvan AS
TitleATP-binding site of adenylate kinase: mechanistic implications of its homology with ras-encoded p21, F1-ATPase, and other nucleotide-binding proteins.
Related Swiss-protP00571
[5]
PubMed ID3023080
JournalEur J Biochem
Year1986
Volume161
Pages127-32
AuthorsSchulz GE, Schiltz E, Tomasselli AG, Frank R, Brune M, Wittinghofer A, Schirmer RH
TitleStructural relationships in the adenylate kinase family.
[6]
PubMed ID3023140
JournalFEBS Lett
Year1986
Volume208
Pages301-4
AuthorsDreusicke D, Schulz GE
TitleThe glycine-rich loop of adenylate kinase forms a giant anion hole.
[7]
PubMed ID2821281
JournalJ Mol Biol
Year1987
Volume195
Pages649-58
AuthorsEgner U, Tomasselli AG, Schulz GE
TitleStructure of the complex of yeast adenylate kinase with the inhibitor P1,P5-di(adenosine-5'-)pentaphosphate at 2.6 A resolution.
[8]
PubMed ID2851785
JournalProtein Seq Data Anal
Year1988
Volume1
Pages335-43
AuthorsReuner C, Hable M, Wilmanns M, Kiefer E, Schiltz E, Schulz GE
TitleAmino acid sequence and three-dimensional structure of cytosolic adenylate kinase from carp muscle.
[9]
PubMed ID2832612
JournalJ Mol Biol
Year1988
Volume199
Pages359-71
AuthorsDreusicke D, Karplus PA, Schulz GE
TitleRefined structure of porcine cytosolic adenylate kinase at 2.1 A resolution.
Related PDB3adk
Related Swiss-protP00571
[10]
PubMed ID2846042
JournalBiochemistry
Year1988
Volume27
Pages5544-52
AuthorsTian GC, Sanders CR 2nd, Kishi F, Nakazawa A, Tsai MD
TitleMechanism of adenylate kinase. Histidine-36 is not directly involved in catalysis, but protects cysteine-25 and stabilizes the tertiary structure.
[11]
PubMed ID2845103
JournalJ Mol Biol
Year1988
Volume202
Pages909-12
AuthorsMuller CW, Schulz GE
TitleStructure of the complex of adenylate kinase from Escherichia coli with the inhibitor P1,P5-di(adenosine-5'-)pentaphosphate.
[12]
PubMed ID2850368
JournalJ Mol Biol
Year1988
Volume203
Pages1021-8
AuthorsDreusicke D, Schulz GE
TitleThe switch between two conformations of adenylate kinase.
[13]
PubMed ID2223776
JournalBiochemistry
Year1990
Volume29
Pages7451-9
AuthorsReinstein J, Schlichting I, Wittinghofer A
TitleStructurally and catalytically important residues in the phosphate binding loop of adenylate kinase of Escherichia coli.
Related Swiss-protP69441
[14]
PubMed ID2162964
JournalJ Mol Biol
Year1990
Volume213
Pages627-30
AuthorsSchulz GE, Muller CW, Diederichs K
TitleInduced-fit movements in adenylate kinases.
[15]
PubMed ID2175649
JournalBiochemistry
Year1990
Volume29
Pages8138-44
AuthorsDiederichs K, Schulz GE
TitleThree-dimensional structure of the complex between the mitochondrial matrix adenylate kinase and its substrate AMP.
[16]
PubMed ID1994037
JournalJ Mol Biol
Year1991
Volume217
Pages541-9
AuthorsDiederichs K, Schulz GE
TitleThe refined structure of the complex between adenylate kinase from beef heart mitochondrial matrix and its substrate AMP at 1.85 A resolution.
[17]
PubMed ID2036423
JournalBiochemistry
Year1991
Volume30
Pages5539-46
AuthorsYan HG, Tsai MD
TitleMechanism of adenylate kinase. Demonstration of a functional relationship between aspartate 93 and Mg2+ by site-directed mutagenesis and proton, phosphorus-31, and magnesium-25 NMR.
[18]
PubMed ID2069947
JournalBiochemistry
Year1991
Volume30
Pages6806-18
AuthorsTsai MD, Yan HG
TitleMechanism of adenylate kinase: site-directed mutagenesis versus X-ray and NMR.
[19]
PubMed ID1548697
JournalJ Mol Biol
Year1992
Volume224
Pages159-77
AuthorsMuller CW, Schulz GE
TitleStructure of the complex between adenylate kinase from Escherichia coli and the inhibitor Ap5A refined at 1.9 A resolution. A model for a catalytic transition state.
Related PDB1ake
Related Swiss-protP69441
[20]
PubMed ID8451239
JournalProteins
Year1993
Volume15
Pages42-9
AuthorsMuller CW, Schulz GE
TitleCrystal structures of two mutants of adenylate kinase from Escherichia coli that modify the Gly-loop.
Related PDB1e4v,1e4y
Related Swiss-protP69441
[21]
PubMed ID8429559
JournalJ Mol Biol
Year1993
Volume229
Pages494-501
AuthorsGerstein M, Schulz G, Chothia C
TitleDomain closure in adenylate kinase. Joints on either side of two helices close like neighboring fingers.
[22]
PubMed ID7880812
JournalBiochemistry
Year1995
Volume34
Pages3172-82
AuthorsByeon L, Shi Z, Tsai MD
TitleMechanism of adenylate kinase. The "essential lysine" helps to orient the phosphates and the active site residues to proper conformations.
[23]
PubMed ID7937733
JournalProteins
Year1994
Volume19
Pages183-98
AuthorsBerry MB, Meador B, Bilderback T, Liang P, Glaser M, Phillips GN Jr
TitleThe closed conformation of a highly flexible protein: the structure of E. coli adenylate kinase with bound AMP and AMPPNP.
Related PDB1ank,1eck,2eck
[24]
PubMed ID7663945
JournalStructure
Year1995
Volume3
Pages483-90
AuthorsVonrhein C, Schlauderer GJ, Schulz GE
TitleMovie of the structural changes during a catalytic cycle of nucleoside monophosphate kinases.
[25]
PubMed ID7635152
JournalEur J Biochem
Year1995
Volume231
Pages405-13
AuthorsSpuergin P, Abele U, Schulz GE
TitleStability, activity and structure of adenylate kinase mutants.
Related PDB3aky
[26]
PubMed ID7670369
JournalProtein Sci
Year1995
Volume4
Pages1262-71
AuthorsAbele U, Schulz GE
TitleHigh-resolution structures of adenylate kinase from yeast ligated with inhibitor Ap5A, showing the pathway of phosphoryl transfer.
Related PDB1aky,2aky
Related Swiss-protP07170
[27]
PubMed ID8805521
JournalStructure
Year1996
Volume4
Pages147-56
AuthorsMuller CW, Schlauderer GJ, Reinstein J, Schulz GE
TitleAdenylate kinase motions during catalysis: an energetic counterweight balancing substrate binding.
Related PDB4ake
[28]
PubMed ID8594191
JournalJ Mol Biol
Year1996
Volume256
Pages223-7
AuthorsSchlauderer GJ, Proba K, Schulz GE
TitleStructure of a mutant adenylate kinase ligated with an ATP-analogue showing domain closure over ATP.
Related PDB1dvr
[29]
PubMed ID8868479
JournalProtein Sci
Year1996
Volume5
Pages434-41
AuthorsSchlauderer GJ, Schulz GE
TitleThe structure of bovine mitochondrial adenylate kinase: comparison with isoenzymes in other compartments.
Related PDB1ak2,2ak2
Related Swiss-protP08166
[30]
PubMed ID9428681
JournalEur J Biochem
Year1997
Volume250
Pages326-31
AuthorsWild K, Grafmuller R, Wagner E, Schulz GE
TitleStructure, catalysis and supramolecular assembly of adenylate kinase from maize.
[31]
PubMed ID9715904
JournalProteins
Year1998
Volume32
Pages276-88
AuthorsBerry MB, Phillips GN Jr
TitleCrystal structures of Bacillus stearothermophilus adenylate kinase with bound Ap5A, Mg2+ Ap5A, and Mn2+ Ap5A reveal an intermediate lid position and six coordinate octahedral geometry for bound Mg2+ and Mn2+.
Related PDB1zio,1zip,1zin
Related Swiss-protP27142
[32]
PubMed ID9733648
JournalJ Mol Biol
Year1998
Volume282
Pages167-79
AuthorsVonrhein C, Bonisch H, Schafer G, Schulz GE
TitleThe structure of a trimeric archaeal adenylate kinase.
Related PDB1nks
Related Swiss-protP35028
[33]
PubMed ID9844727
JournalBiochem Mol Biol Int
Year1998
Volume46
Pages673-80
AuthorsAyabe T, Park SK, Nagahama H, Maruyama H, Sumida M, Takenaka H, Takenaka O, Onitsuka T, Hamada M
TitleSite-directed mutagenesis and steady-state kinetic analysis of mutant enzymes of human adenylate kinase.
[34]
PubMed ID10491122
JournalEur J Biochem
Year1999
Volume264
Pages765-74
AuthorsBurlacu-Miron S, Gilles AM, Popescu A, Barzu O, Craescu CT
TitleMultinuclear magnetic resonance studies of Escherichia coli adenylate kinase in free and bound forms. Resonance assignment, secondary structure and ligand binding.
[35]
PubMed ID11976328
JournalJ Biol Chem
Year2002
Volume277
Pages25685-91
AuthorsAddona GH, Husain SS, Stehle T, Miller KW
TitleGeometric isomers of a photoactivable general anesthetic delineate a binding site on adenylate kinase.
[36]
PubMed ID19805185
JournalProc Natl Acad Sci U S A
Year2009
Volume106
Pages16984-9
AuthorsSchrank TP, Bolen DW, Hilser VJ
TitleRational modulation of conformational fluctuations in adenylate kinase reveals a local unfolding mechanism for allostery and functional adaptation in proteins.
Related PDB3hpq,3hpr

comments
This enzyme is homologous to the counterpart enzymes (S00547 and S00548 in EzCatDB).
The counterpart enzyme from archaean species (PDB; 1nks) seems to be distinct from others, and catalytic residues are not so conserved (see [32]; S00548).
The literature [12], [14], [21], [23], [24] & [27] reported that conformational change occurs upon substrate binding and during catalysis.
The transfer reaction of the gamma-phosphoryl group of ATP occurs by an in-line mechanism involving a tentacovalent-transition-state with the nucleophilic acceptor group, the oxygen atom of the phosphate group of AMP, and the leaving group, the beta-phosphate of ATP in the two apical positions (see [19]). The paper [26] suggested that the in-line phosphoryl transfer is associative (SN2-like).
The transferred phosphoryl group is stabilized by conserved residues, Lys13, Arg156 and Arg167 (of 1ake). The acceptor phosphoryl group is stabilized by Arg36 and Arg88.
The role of cofactor, magnesium ion, which is bound to Asp84 (of 1ake), is discussed in the papers [17] & [31], as follows:
(1) This ion shield the negative charge of the transferred group, the gamma-phosphate of ATP from the attacking nucleophile, the acceptor oxygen atom of the alpha-phosphate of AMP, by its interaction with the gamma-phosphate.
(2) This ion enhances the cleavage of the P(gamma)-O bond by electrophilic effects.
(3) This ion orients the phosphate chain in proper positions.

createdupdated
2002-05-312010-05-20
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)

© Computational Biology Research Center, AIST, 2004 All Rights Reserved.