DB code: S00305

RLCP classification 3.133.90010.394 : Transfer
CATH domain 3.40.50.300 : Rossmann fold Catalytic domain
E.C. 2.7.4.3
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.40.50.300 : Rossmann fold S00527 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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P69441 Adenylate kinase
AK
EC 2.7.4.3
ATP-AMP transphosphorylase
NP_415007.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_488765.1 (Protein)
NC_007779.1 (DNA/RNA sequence)
PF00406 (ADK)
PF05191 (ADK_lid)
[Graphical View]
P07170 Adenylate kinase 1
AK 1
EC 2.7.4.3
ATP-AMP transphosphorylase 1
Adenylate kinase cytosolic and mitochondrial
NP_010512.1 (Protein)
NM_001180534.1 (DNA/RNA sequence)
PF00406 (ADK)
PF05191 (ADK_lid)
[Graphical View]
P00571 Adenylate kinase isoenzyme 1
AK 1
EC 2.7.4.3
ATP-AMP transphosphorylase 1
Myokinase
XP_003122225.3 (Protein)
XM_003122177.3 (DNA/RNA sequence)
PF00406 (ADK)
[Graphical View]
P08166 Adenylate kinase 2, mitochondrial
AK 2
EC 2.7.4.3
ATP-AMP transphosphorylase 2
NP_776314.1 (Protein)
NM_173889.1 (DNA/RNA sequence)
PF00406 (ADK)
PF05191 (ADK_lid)
[Graphical View]

KEGG enzyme name
adenylokinase
adenylate kinase
myokinase
5'-AMP-kinase
adenylic kinase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P69441 KAD_ECOLI ATP + AMP = 2 ADP. Monomer. Cytoplasm.
P07170 KAD1_YEAST ATP + AMP = 2 ADP. Monomer. Cytoplasm.
P00571 KAD1_PIG ATP + AMP = 2 ADP. Monomer. Cytoplasm.
P08166 KAD2_BOVIN ATP + AMP = 2 ADP. Monomer. Mitochondrion intermembrane space.

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

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00002 C00020 C00008 C00008
E.C.
Compound Magnesium ATP AMP ADP (from ATP) ADP (from AMP)
Type divalent metal (Ca2+, Mg2+) amine group,nucleotide amine group,nucleotide amine group,nucleotide amine group,nucleotide
ChEBI 18420
 18420
 		15422
 15422
 		16027
 16027
 		16761
 16761
 		16761
 16761
PubChem 888
 888
 		5957
 5957
 		6083
 6083
 		6022
 6022
 		6022
 6022
1akeA Unbound Analogue:AP5(ATP) Analogue:AP5(AMP) Unbound Unbound
1akeB Unbound Analogue:AP5(ATP) Analogue:AP5(AMP) Unbound Unbound
1ankA Unbound Analogue:ANP Bound:AMP Unbound Unbound
1ankB Unbound Analogue:ANP Bound:AMP Unbound Unbound
1e4vA Unbound Analogue:AP5(ATP) Analogue:AP5(AMP) Unbound Unbound
1e4vB Unbound Analogue:AP5(ATP) Analogue:AP5(AMP) Unbound Unbound
1e4yA Unbound Analogue:AP5(ATP) Analogue:AP5(AMP) Unbound Unbound
1e4yB Unbound Analogue:AP5(ATP) Analogue:AP5(AMP) Unbound Unbound
1eckA Unbound Unbound Bound:AMP Bound:ADP Unbound
1eckB Unbound Unbound Bound:AMP Bound:ADP Unbound
2eckA Unbound Unbound Bound:AMP Bound:ADP Unbound
2eckB Unbound Unbound Bound:AMP Bound:ADP Unbound
3hpqA Unbound Analogue:AP5(ATP) Analogue:AP5(AMP) Unbound Unbound
3hpqB Unbound Analogue:AP5(ATP) Analogue:AP5(AMP) Unbound Unbound
3hprA Unbound Analogue:AP5(ATP) Analogue:AP5(AMP) Unbound Unbound
3hprB Unbound Analogue:AP5(ATP) Analogue:AP5(AMP) Unbound Unbound
4akeA Unbound Unbound Unbound Unbound Unbound
4akeB Unbound Unbound Unbound Unbound Unbound
1akyA Unbound Analogue:AP5(ATP) Analogue:AP5(AMP) Unbound Unbound
1dvrA Unbound Analogue:ATF Unbound Unbound Unbound
1dvrB Unbound Analogue:ATF Unbound Unbound Unbound
2akyA Bound:_MG Analogue:AP5(ATP) Analogue:AP5(AMP) Unbound Unbound
3akyA Unbound Analogue:AP5(ATP) Analogue:AP5(AMP) Unbound Unbound
1ak2A Unbound Unbound Unbound Unbound Unbound
2ak2A Unbound Unbound Unbound Unbound Unbound
3adkA Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [17], [18] & [19]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1akeA LYS 13;ARG 36;ARG 88;ARG 156;ARG 167 ASP 84(magnesium binding)
1akeB LYS 13;ARG 36;ARG 88;ARG 156;ARG 167 ASP 84(magnesium binding)
1ankA LYS 13;ARG 36;ARG 88;ARG 156;ARG 167 ASP 84(magnesium binding)
1ankB LYS 13;ARG 36;ARG 88;ARG 156;ARG 167 ASP 84(magnesium binding)
1e4vA LYS 13;ARG 36;ARG 88;ARG 156;ARG 167 ASP 84(magnesium binding)
1e4vB LYS 13;ARG 36;ARG 88;ARG 156;ARG 167 ASP 84(magnesium binding)
1e4yA LYS 13;ARG 36;ARG 88;ARG 156;ARG 167 ASP 84(magnesium binding)
1e4yB LYS 13;ARG 36;ARG 88;ARG 156;ARG 167 ASP 84(magnesium binding)
1eckA LYS 13;ARG 36;ARG 88;ARG 156;ARG 167 ASP 84(magnesium binding)
1eckB LYS 13;ARG 36;ARG 88;ARG 156;ARG 167 ASP 84(magnesium binding)
2eckA LYS 13;ARG 36;ARG 88;ARG 156;ARG 167 ASP 84(magnesium binding)
2eckB LYS 13;ARG 36;ARG 88;ARG 156;ARG 167 ASP 84(magnesium binding)
3hpqA LYS 13;ARG 36;ARG 88;ARG 156;ARG 167 ASP 84(magnesium binding)
3hpqB LYS 13;ARG 36;ARG 88;ARG 156;ARG 167 ASP 84(magnesium binding)
3hprA LYS 13;ARG 36;ARG 88;ARG 156;ARG 167 ASP 84(magnesium binding) mutant V148G
3hprB LYS 13;ARG 36;ARG 88;ARG 156;ARG 167 ASP 84(magnesium binding) mutant V148G
4akeA LYS 13;ARG 36;ARG 88;ARG 156;ARG 167 ASP 84(magnesium binding)
4akeB LYS 13;ARG 36;ARG 88;ARG 156;ARG 167 ASP 84(magnesium binding)
1akyA LYS 17;ARG 40;ARG 93;ARG 165;ARG 176 ASP 89(magnesium binding)
1dvrA LYS 17;ARG 40;ARG 93; ;ARG 176 mutant D89V, R165I
1dvrB LYS 17;ARG 40;ARG 93; ;ARG 176 mutant D89V, R165I
2akyA LYS 17;ARG 40;ARG 93;ARG 165;ARG 176 ASP 89(magnesium binding)
3akyA LYS 17;ARG 40;ARG 93;ARG 165;ARG 176 ASP 89(magnesium binding)
1ak2A LYS 29;ARG 52;ARG 104;ARG 176;ARG 187 ASP 100(magnesium binding)
2ak2A LYS 29;ARG 52;ARG 104;ARG 176;ARG 187 ASP 100(magnesium binding)
3adkA LYS 21;ARG 44;ARG 97;ARG 138;ARG 149 ASP 93(magnesium binding)

References for Catalytic Mechanism
References Sections No. 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]
Resource
Comments
Medline ID
PubMed ID 4367210
Journal Nature
Year 1974
Volume 250
Pages 120-3
Authors Schulz GE, Elzinga M, Marx F, Schrimer RH
Title Three dimensional structure of adenyl kinase.
Related PDB P00571
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 6086335
Journal Eur J Biochem
Year 1984
Volume 141
Pages 629-36
Authors Frank R, Trosin M, Tomasselli AG, Schulz GE, Schirmer RH
Title Mitochondrial adenylate kinase (AK2) from bovine heart. Homology with the cytosolic isoenzyme in the catalytic region.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 3002789
Journal Eur J Biochem
Year 1986
Volume 154
Pages 205-11
Authors Frank R, Trosin M, Tomasselli AG, Noda L, Krauth-Siegel RL, Schirmer RH
Title Mitochondrial adenylate kinase (AK2) from bovine heart. The complete primary structure.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 2869483
Journal Proc Natl Acad Sci U S A
Year 1986
Volume 83
Pages 907-11
Authors Fry DC, Kuby SA, Mildvan AS
Title ATP-binding site of adenylate kinase: mechanistic implications of its homology with ras-encoded p21, F1-ATPase, and other nucleotide-binding proteins.
Related PDB
Related UniProtKB P00571
[5]
Resource
Comments
Medline ID
PubMed ID 3023080
Journal Eur J Biochem
Year 1986
Volume 161
Pages 127-32
Authors Schulz GE, Schiltz E, Tomasselli AG, Frank R, Brune M, Wittinghofer A, Schirmer RH
Title Structural relationships in the adenylate kinase family.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 3023140
Journal FEBS Lett
Year 1986
Volume 208
Pages 301-4
Authors Dreusicke D, Schulz GE
Title The glycine-rich loop of adenylate kinase forms a giant anion hole.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 2821281
Journal J Mol Biol
Year 1987
Volume 195
Pages 649-58
Authors Egner U, Tomasselli AG, Schulz GE
Title Structure of the complex of yeast adenylate kinase with the inhibitor P1,P5-di(adenosine-5'-)pentaphosphate at 2.6 A resolution.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 2851785
Journal Protein Seq Data Anal
Year 1988
Volume 1
Pages 335-43
Authors Reuner C, Hable M, Wilmanns M, Kiefer E, Schiltz E, Schulz GE
Title Amino acid sequence and three-dimensional structure of cytosolic adenylate kinase from carp muscle.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 2832612
Journal J Mol Biol
Year 1988
Volume 199
Pages 359-71
Authors Dreusicke D, Karplus PA, Schulz GE
Title Refined structure of porcine cytosolic adenylate kinase at 2.1 A resolution.
Related PDB 3adk
Related UniProtKB P00571
[10]
Resource
Comments
Medline ID
PubMed ID 2846042
Journal Biochemistry
Year 1988
Volume 27
Pages 5544-52
Authors Tian GC, Sanders CR 2nd, Kishi F, Nakazawa A, Tsai MD
Title Mechanism of adenylate kinase. Histidine-36 is not directly involved in catalysis, but protects cysteine-25 and stabilizes the tertiary structure.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 2845103
Journal J Mol Biol
Year 1988
Volume 202
Pages 909-12
Authors Muller CW, Schulz GE
Title Structure of the complex of adenylate kinase from Escherichia coli with the inhibitor P1,P5-di(adenosine-5'-)pentaphosphate.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 2850368
Journal J Mol Biol
Year 1988
Volume 203
Pages 1021-8
Authors Dreusicke D, Schulz GE
Title The switch between two conformations of adenylate kinase.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 2223776
Journal Biochemistry
Year 1990
Volume 29
Pages 7451-9
Authors Reinstein J, Schlichting I, Wittinghofer A
Title Structurally and catalytically important residues in the phosphate binding loop of adenylate kinase of Escherichia coli.
Related PDB
Related UniProtKB P69441
[14]
Resource
Comments
Medline ID
PubMed ID 2162964
Journal J Mol Biol
Year 1990
Volume 213
Pages 627-30
Authors Schulz GE, Muller CW, Diederichs K
Title Induced-fit movements in adenylate kinases.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 2175649
Journal Biochemistry
Year 1990
Volume 29
Pages 8138-44
Authors Diederichs K, Schulz GE
Title Three-dimensional structure of the complex between the mitochondrial matrix adenylate kinase and its substrate AMP.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 1994037
Journal J Mol Biol
Year 1991
Volume 217
Pages 541-9
Authors Diederichs K, Schulz GE
Title The refined structure of the complex between adenylate kinase from beef heart mitochondrial matrix and its substrate AMP at 1.85 A resolution.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 2036423
Journal Biochemistry
Year 1991
Volume 30
Pages 5539-46
Authors Yan HG, Tsai MD
Title Mechanism 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.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 2069947
Journal Biochemistry
Year 1991
Volume 30
Pages 6806-18
Authors Tsai MD, Yan HG
Title Mechanism of adenylate kinase: site-directed mutagenesis versus X-ray and NMR.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 1548697
Journal J Mol Biol
Year 1992
Volume 224
Pages 159-77
Authors Muller CW, Schulz GE
Title Structure 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 PDB 1ake
Related UniProtKB P69441
[20]
Resource
Comments
Medline ID
PubMed ID 8451239
Journal Proteins
Year 1993
Volume 15
Pages 42-9
Authors Muller CW, Schulz GE
Title Crystal structures of two mutants of adenylate kinase from Escherichia coli that modify the Gly-loop.
Related PDB 1e4v 1e4y
Related UniProtKB P69441
[21]
Resource
Comments
Medline ID
PubMed ID 8429559
Journal J Mol Biol
Year 1993
Volume 229
Pages 494-501
Authors Gerstein M, Schulz G, Chothia C
Title Domain closure in adenylate kinase. Joints on either side of two helices close like neighboring fingers.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 7880812
Journal Biochemistry
Year 1995
Volume 34
Pages 3172-82
Authors Byeon L, Shi Z, Tsai MD
Title Mechanism of adenylate kinase. The "essential lysine" helps to orient the phosphates and the active site residues to proper conformations.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 7937733
Journal Proteins
Year 1994
Volume 19
Pages 183-98
Authors Berry MB, Meador B, Bilderback T, Liang P, Glaser M, Phillips GN Jr
Title The closed conformation of a highly flexible protein: the structure of E. coli adenylate kinase with bound AMP and AMPPNP.
Related PDB 1ank 1eck 2eck
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 7663945
Journal Structure
Year 1995
Volume 3
Pages 483-90
Authors Vonrhein C, Schlauderer GJ, Schulz GE
Title Movie of the structural changes during a catalytic cycle of nucleoside monophosphate kinases.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 7635152
Journal Eur J Biochem
Year 1995
Volume 231
Pages 405-13
Authors Spuergin P, Abele U, Schulz GE
Title Stability, activity and structure of adenylate kinase mutants.
Related PDB 3aky
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 7670369
Journal Protein Sci
Year 1995
Volume 4
Pages 1262-71
Authors Abele U, Schulz GE
Title High-resolution structures of adenylate kinase from yeast ligated with inhibitor Ap5A, showing the pathway of phosphoryl transfer.
Related PDB 1aky 2aky
Related UniProtKB P07170
[27]
Resource
Comments
Medline ID
PubMed ID 8805521
Journal Structure
Year 1996
Volume 4
Pages 147-56
Authors Muller CW, Schlauderer GJ, Reinstein J, Schulz GE
Title Adenylate kinase motions during catalysis: an energetic counterweight balancing substrate binding.
Related PDB 4ake
Related UniProtKB
[28]
Resource
Comments
Medline ID
PubMed ID 8594191
Journal J Mol Biol
Year 1996
Volume 256
Pages 223-7
Authors Schlauderer GJ, Proba K, Schulz GE
Title Structure of a mutant adenylate kinase ligated with an ATP-analogue showing domain closure over ATP.
Related PDB 1dvr
Related UniProtKB
[29]
Resource
Comments
Medline ID
PubMed ID 8868479
Journal Protein Sci
Year 1996
Volume 5
Pages 434-41
Authors Schlauderer GJ, Schulz GE
Title The structure of bovine mitochondrial adenylate kinase: comparison with isoenzymes in other compartments.
Related PDB 1ak2 2ak2
Related UniProtKB P08166
[30]
Resource
Comments
Medline ID
PubMed ID 9428681
Journal Eur J Biochem
Year 1997
Volume 250
Pages 326-31
Authors Wild K, Grafmuller R, Wagner E, Schulz GE
Title Structure, catalysis and supramolecular assembly of adenylate kinase from maize.
Related PDB
Related UniProtKB
[31]
Resource
Comments
Medline ID
PubMed ID 9715904
Journal Proteins
Year 1998
Volume 32
Pages 276-88
Authors Berry MB, Phillips GN Jr
Title Crystal 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 PDB 1zio 1zip 1zin
Related UniProtKB P27142
[32]
Resource
Comments
Medline ID
PubMed ID 9733648
Journal J Mol Biol
Year 1998
Volume 282
Pages 167-79
Authors Vonrhein C, Bonisch H, Schafer G, Schulz GE
Title The structure of a trimeric archaeal adenylate kinase.
Related PDB 1nks
Related UniProtKB P35028
[33]
Resource
Comments
Medline ID
PubMed ID 9844727
Journal Biochem Mol Biol Int
Year 1998
Volume 46
Pages 673-80
Authors Ayabe T, Park SK, Nagahama H, Maruyama H, Sumida M, Takenaka H, Takenaka O, Onitsuka T, Hamada M
Title Site-directed mutagenesis and steady-state kinetic analysis of mutant enzymes of human adenylate kinase.
Related PDB
Related UniProtKB
[34]
Resource
Comments
Medline ID
PubMed ID 10491122
Journal Eur J Biochem
Year 1999
Volume 264
Pages 765-74
Authors Burlacu-Miron S, Gilles AM, Popescu A, Barzu O, Craescu CT
Title Multinuclear magnetic resonance studies of Escherichia coli adenylate kinase in free and bound forms. Resonance assignment, secondary structure and ligand binding.
Related PDB
Related UniProtKB
[35]
Resource
Comments
Medline ID
PubMed ID 11976328
Journal J Biol Chem
Year 2002
Volume 277
Pages 25685-91
Authors Addona GH, Husain SS, Stehle T, Miller KW
Title Geometric isomers of a photoactivable general anesthetic delineate a binding site on adenylate kinase.
Related PDB
Related UniProtKB
[36]
Resource
Comments
Medline ID
PubMed ID 19805185
Journal Proc Natl Acad Sci U S A
Year 2009
Volume 106
Pages 16984-9
Authors Schrank TP, Bolen DW, Hilser VJ
Title Rational modulation of conformational fluctuations in adenylate kinase reveals a local unfolding mechanism for allostery and functional adaptation in proteins.
Related PDB 3hpq 3hpr
Related UniProtKB

Comments
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.
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 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.

Created Updated
2002-05-31 2010-05-20