DB code: M00200

RLCP classification 3.103.90020.1136 : Transfer
CATH domain -.-.-.- :
-.-.-.- :
3.30.70.1230 : Alpha-Beta Plaits Catalytic domain
-.-.-.- :
3.30.70.1230 : Alpha-Beta Plaits Catalytic domain
E.C. 4.6.1.1
CSA 1ab8
M-CSA 1ab8
MACiE M0058

CATH domain Related DB codes (homologues)
3.30.70.1230 : Alpha-Beta Plaits M00201

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P30803 Adenylate cyclase type 5
EC 4.6.1.1
Adenylate cyclase type V
ATP pyrophosphate-lyase 5
Adenylyl cyclase 5
Ca(2+)-inhibitable adenylyl cyclase
NP_001161932.1 (Protein)
NM_001168460.1 (DNA/RNA sequence)
PF06327 (DUF1053)
PF00211 (Guanylate_cyc)
[Graphical View]
P26769 Adenylate cyclase type 2
EC 4.6.1.1
Adenylate cyclase type II
ATP pyrophosphate-lyase 2
Adenylyl cyclase 2
NP_112269.1 (Protein)
NM_031007.1 (DNA/RNA sequence)
PF06327 (DUF1053)
PF00211 (Guanylate_cyc)
[Graphical View]

KEGG enzyme name
adenylate cyclase
adenylylcyclase
adenyl cyclase
3',5'-cyclic AMP synthetase
ATP diphosphate-lyase (cyclizing)

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P30803 ADCY5_CANFA ATP = 3'',5''-cyclic AMP + diphosphate. Membrane, Multi-pass membrane protein. Binds 2 magnesium ions per subunit.
P26769 ADCY2_RAT ATP = 3'',5''-cyclic AMP + diphosphate. Membrane, Multi-pass membrane protein. Binds 2 magnesium ions per subunit (By similarity).

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

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00002 C00131 C00575 C00968 C00013
E.C.
Compound Magnesium ATP dATP 3',5'-Cyclic AMP 3',5'-Cyclic dAMP Pyrophosphate
Type divalent metal (Ca2+, Mg2+) amine group,nucleotide amine group,nucleotide amine group,nucleotide amine group,nucleotide phosphate group/phosphate ion
ChEBI 18420
15422
16284
17489
28074
29888
PubChem 888
5957
15993
6076
188955
1023
21961011
1azsA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1cjkA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:_MG-_MN Analogue:AGS Unbound Unbound Unbound Unbound
1cjtA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:_MG-_MN Unbound Analogue:DAD Unbound Unbound Unbound
1cjuA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_MG Unbound Analogue:DAD Unbound Unbound Unbound
1cjvA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:_MG-_ZN Unbound Analogue:DAD Unbound Unbound Unbound
1cs4A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:_MG Unbound Unbound Unbound Unbound Bound:POP
1culA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_MG Unbound Unbound Unbound Unbound Analogue:3PO
1tl7A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:2x_MN Analogue:ONM Unbound Unbound Unbound Unbound
1u0hA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_MG Analogue:ONM Unbound Unbound Unbound Unbound
2gvdA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:2x_MN Analogue:128 Unbound Unbound Unbound Unbound
2gvzA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:2x_MN Analogue:ONA Unbound Unbound Unbound Unbound
1ab8A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1ab8B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1azsB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1cjkB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1cjtB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1cjuB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1cjvB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1cs4B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:101 Unbound
1culB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:103 Unbound
1tl7B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1u0hB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
2gvdB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
2gvzB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [12]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1azsA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 484 ASP 396;ILE 397;ASP 440(Magnesium binding) mutant V476M
1cjkA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 484 ASP 396;ILE 397;ASP 440(Magnesium binding)
1cjtA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 484 ASP 396;ILE 397;ASP 440(Magnesium binding)
1cjuA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 484 ASP 396;ILE 397;ASP 440(Magnesium binding)
1cjvA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 484 ASP 396;ILE 397;ASP 440(Magnesium binding)
1cs4A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 484 ASP 396;ILE 397;ASP 440(Magnesium binding)
1culA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 484 ASP 396;ILE 397;ASP 440(Magnesium binding)
1tl7A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 484 ASP 396;ILE 397;ASP 440(Magnesium binding)
1u0hA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 484 ASP 396;ILE 397;ASP 440(Magnesium binding)
2gvdA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 484 ASP 396;ILE 397;ASP 440(Magnesium binding)
2gvzA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 484 ASP 396;ILE 397;ASP 440(Magnesium binding)
1ab8A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 1029; invisible 1059-1073
1ab8B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 1029; invisible 1059-1073
1azsB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 1029;LYS 1065
1cjkB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 1029;LYS 1065
1cjtB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 1029;LYS 1065
1cjuB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 1029;LYS 1065
1cjvB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 1029;LYS 1065
1cs4B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 1029;LYS 1065
1culB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 1029;LYS 1065
1tl7B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 1029;LYS 1065
1u0hB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 1029;LYS 1065
2gvdB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 1029;LYS 1065
2gvzB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ARG 1029;LYS 1065

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[9]
p.33
[7]
Fig.7, p.13419
[10]
Fig.6, p1914-1915
[12]
Fig.3, p.715-716
[14]
Fig.4, p.19654 1
[15]
p.237
[17]
Fig.2, p.7600 3
[18]
Fig.1, p.757-759

References
[1]
Resource
Comments
Medline ID
PubMed ID 1525824
Journal Cell
Year 1992
Volume 70
Pages 869-72
Authors Tang WJ, Gilman AG
Title Adenylyl cyclases.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 8418825
Journal Adv Second Messenger Phosphoprotein Res
Year 1993
Volume 27
Pages 109-62
Authors Danchin A
Title Phylogeny of adenylyl cyclases.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 9048648
Journal Circ Res
Year 1997
Volume 80
Pages 297-304
Authors Ishikawa Y, Homcy CJ
Title The adenylyl cyclases as integrators of transmembrane signal transduction.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 9346923
Journal J Biol Chem
Year 1997
Volume 272
Pages 27787-95
Authors Dessauer CW, Gilman AG
Title The catalytic mechanism of mammalian adenylyl cyclase. Equilibrium binding and kinetic analysis of P-site inhibition.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 9214499
Journal Nature
Year 1997
Volume 388
Pages 33-4
Authors Artymiuk PJ, Poirrette AR, Rice DW, Willett P
Title A polymerase I palm in adenylyl cyclase?
Related PDB
Related UniProtKB
[6]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.58 ANGSTROMS) OF 871-1090.
Medline ID 97222132
PubMed ID 9069282
Journal Nature
Year 1997
Volume 386
Pages 247-53
Authors Zhang G, Liu Y, Ruoho AE, Hurley JH
Title Structure of the adenylyl cyclase catalytic core.
Related PDB 1ab8
Related UniProtKB P26769
[7]
Resource
Comments
Medline ID
PubMed ID 9391039
Journal Proc Natl Acad Sci U S A
Year 1997
Volume 94
Pages 13414-9
Authors Liu Y, Ruoho AE, Rao VD, Hurley JH
Title Catalytic mechanism of the adenylyl and guanylyl cyclases: modeling and mutational analysis.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 9098900
Journal Protein Sci
Year 1997
Volume 6
Pages 903-8
Authors Zhang G, Liu Y, Qin J, Vo B, Tang WJ, Ruoho AE, Hurley JH
Title Characterization and crystallization of a minimal catalytic core domain from mammalian type II adenylyl cyclase.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 9417637
Journal Science
Year 1997
Volume 278
Pages 1898-9
Authors Bourne HR
Title Pieces of the true grail: a G protein finds its target.
Related PDB
Related UniProtKB
[10]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 870-1081 OF COMPLEX WITH G(S)-ALPHA.
Medline ID 98072190
PubMed ID 9417641
Journal Science
Year 1997
Volume 278
Pages 1907-16
Authors Tesmer JJ, Sunahara RK, Gilman AG, Sprang SR
Title Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gsalpha.GTPgammaS.
Related PDB 1azs
Related UniProtKB P26769 P30803
[11]
Resource
Comments
Medline ID
PubMed ID 9819210
Journal Biochemistry
Year 1998
Volume 37
Pages 16183-91
Authors Mitterauer T, Hohenegger M, Tang WJ, Nanoff C, Freissmuth M
Title The C2 catalytic domain of adenylyl cyclase contains the second metal ion (Mn2+) binding site.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 9914249
Journal Curr Opin Struct Biol
Year 1998
Volume 8
Pages 713-9
Authors Tesmer JJ, Sprang SR
Title The structure, catalytic mechanism and regulation of adenylyl cyclase.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 9632695
Journal J Biol Chem
Year 1998
Volume 273
Pages 16332-8
Authors Sunahara RK, Beuve A, Tesmer JJ, Sprang SR, Garbers DL, Gilman AG
Title Exchange of substrate and inhibitor specificities between adenylyl and guanylyl cyclases.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 9677392
Journal J Biol Chem
Year 1998
Volume 273
Pages 19650-5
Authors Zimmermann G, Zhou D, Taussig R
Title Mutations uncover a role for two magnesium ions in the catalytic mechanism of adenylyl cyclase.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 9687563
Journal Mol Pharmacol
Year 1998
Volume 54
Pages 231-40
Authors Tang WJ, Hurley JH
Title Catalytic mechanism and regulation of mammalian adenylyl cyclases.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 10600134
Journal Biochemistry
Year 1999
Volume 38
Pages 16706-13
Authors Tepe NM, Lorenz JN, Yatani A, Dash R, Kranias EG, Dorn GW 2nd, Liggett SB
Title Altering the receptor-effector ratio by transgenic overexpression of type V adenylyl cyclase: enhanced basal catalytic activity and function without increased cardiomyocyte beta-adrenergic signalling.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 10075642
Journal J Biol Chem
Year 1999
Volume 274
Pages 7599-602
Authors Hurley JH
Title Structure, mechanism, and regulation of mammalian adenylyl cyclase.
Related PDB
Related UniProtKB
[18]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 870-1081 OF COMPLEX WITH G(S)-ALPHA.
Medline ID 99357873
PubMed ID 10427002
Journal Science
Year 1999
Volume 285
Pages 756-60
Authors Tesmer JJ, Sunahara RK, Johnson RA, Gosselin G, Gilman AG, Sprang SR
Title Two-metal-Ion catalysis in adenylyl cyclase.
Related PDB 1cjk 1cjt 1cju 1cjv
Related UniProtKB P26769 P30803
[19]
Resource
Comments
Medline ID
PubMed ID 10354616
Journal Trends Pharmacol Sci
Year 1999
Volume 20
Pages 205-10
Authors Dessauer CW, Tesmer JJ, Sprang SR, Gilman AG
Title The interactions of adenylate cyclases with P-site inhibitors.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 10101967
Journal Trends Pharmacol Sci
Year 1999
Volume 20
Pages 66-73
Authors Simonds WF
Title G protein regulation of adenylate cyclase.
Related PDB
Related UniProtKB
[21]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 11087399
Journal Biochemistry
Year 2000
Volume 39
Pages 14464-71
Authors Tesmer JJ, Dessauer CW, Sunahara RK, Murray LD, Johnson RA, Gilman AG, Sprang SR
Title Molecular basis for P-site inhibition of adenylyl cyclase.
Related PDB 1cs4 1cul
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 11327830
Journal Biochemistry
Year 2001
Volume 40
Pages 1702-9
Authors Tan CM, Kelvin DJ, Litchfield DW, Ferguson SS, Feldman RD
Title Tyrosine kinase-mediated serine phosphorylation of adenylyl cyclase.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 11535062
Journal Biochemistry
Year 2001
Volume 40
Pages 10853-8
Authors Weitmann S, Schultz G, Kleuss C
Title Adenylyl cyclase type II domains involved in Gbetagamma stimulation.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 11461898
Journal J Biol Chem
Year 2001
Volume 276
Pages 35450-7
Authors Wu GC, Lai HL, Lin YW, Chu YT, Chern Y
Title N-glycosylation and residues Asn805 and Asn890 are involved in the functional properties of type VI adenylyl cyclase.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 12372507
Journal Bioorg Med Chem Lett
Year 2002
Volume 12
Pages 3085-8
Authors Levy D, Marlowe C, Kane-Maguire K, Bao M, Cherbavaz D, Tomlinson J, Sedlock D, Scarborough R
Title Hydroxamate based inhibitors of adenylyl cyclase. Part 1: the effect of acyclic linkers on P-site binding.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 12372508
Journal Bioorg Med Chem Lett
Year 2002
Volume 12
Pages 3089-92
Authors Levy D, Bao M, Tomlinson J, Scarborough R
Title Hydroxamate based inhibitors of adenylyl cyclase. Part 2: the effect of cyclic linkers on P-site binding.
Related PDB
Related UniProtKB
[27]
Resource
Comments
Medline ID
PubMed ID 12019229
Journal Genetics
Year 2002
Volume 161
Pages 133-42
Authors Moorman C, Plasterk RH
Title Functional characterization of the adenylyl cyclase gene sgs-1 by analysis of a mutational spectrum in Caenorhabditis elegans.
Related PDB
Related UniProtKB
[28]
Resource
Comments
Medline ID
PubMed ID 12058044
Journal J Biol Chem
Year 2002
Volume 277
Pages 28823-9
Authors Dessauer CW, Chen-Goodspeed M, Chen J
Title Mechanism of Galpha i-mediated inhibition of type V adenylyl cyclase.
Related PDB
Related UniProtKB
[29]
Resource
Comments
Medline ID
PubMed ID 12065575
Journal J Biol Chem
Year 2002
Volume 277
Pages 33139-47
Authors Hu B, Nakata H, Gu C, De Beer T, Cooper DM
Title A critical interplay between Ca2+ inhibition and activation by Mg2+ of AC5 revealed by mutants and chimeric constructs.
Related PDB
Related UniProtKB
[30]
Resource
Comments
Medline ID
PubMed ID 11877398
Journal J Biol Chem
Year 2002
Volume 277
Pages 15721-8
Authors Lin TH, Lai HL, Kao YY, Sun CN, Hwang MJ, Chern Y
Title Protein kinase C inhibits type VI adenylyl cyclase by phosphorylating the regulatory N domain and two catalytic C1 and C2 domains.
Related PDB
Related UniProtKB
[31]
Resource
Comments
Medline ID
PubMed ID 11665600
Journal Methods Enzymol
Year 2002
Volume 345
Pages 127-40
Authors Hatley ME, Gilman AG, Sunahara RK
Title Expression, purification, and assay of cytosolic (catalytic) domains of membrane-bound mammalian adenylyl cyclases.
Related PDB
Related UniProtKB
[32]
Resource
Comments
Medline ID
PubMed ID 11665605
Journal Methods Enzymol
Year 2002
Volume 345
Pages 198-206
Authors Tesmer JJ, Sunahara RK, Fancy DA, Gilman AG, Sprang SR
Title Crystallization of complex between soluble domains of adenylyl cyclase and activated Gs alpha.
Related PDB
Related UniProtKB
[33]
Resource
Comments
Medline ID
PubMed ID 16766715
Journal Mol Pharmacol
Year 2006
Volume 70
Pages 878-86
Authors Mou TC, Gille A, Suryanarayana S, Richter M, Seifert R, Sprang SR
Title Broad specificity of mammalian adenylyl cyclase for interaction with 2',3'-substituted purine- and pyrimidine nucleotide inhibitors.
Related PDB 1tl7 1u0h
Related UniProtKB
[34]
Resource
Comments
Medline ID
PubMed ID 15591060
Journal J Biol Chem
Year 2005
Volume 280
Pages 7253-61
Authors Mou TC, Gille A, Fancy DA, Seifert R, Sprang SR
Title Structural basis for the inhibition of mammalian membrane adenylyl cyclase by 2'(3')-O-(N-Methylanthraniloyl)-guanosine 5 '-triphosphate.
Related PDB 2gvd 2gvz
Related UniProtKB

Comments
There is a variety of adenylyl cyclase enzymes. This enzyme belongs to Class-IV adenylyl cylcase family, which has two catalytic domains. The catalytic domains are homologous to each other, as well as to that of the class-III family.
This enzyme is composed of a short cytoplasmic N-terminal region, two repeats of a unit comprising a membrane-spanning region (M) and two cytoplasmic regions (C) (see [12], [17]). The membrane-spanning regions (M1 and M2) each contain six membrane-spanning helices. The two cytoplasmic regionns (C1 and C2) are subdivided into C1a and C1b; and C2a and C2b. The C1a and C2a are homologous to each other, and contain all of the catalytic apparatus, which heterodimerize with each other (see [12], [17]).
The heterodimer of the C1a and C2a domains has got one catalytic site, which binds one ATP molecule with two magnesium ions.
According to the literature [12] and [14], this enzyme catalyzes the same reaction as that of DNA polymerase, although it catalyzes an intra-molecular phosphoryl transfer reaction, instead of inter-molecular transfer reaction.
(1) The magnesium ion-A, which bound to Asp440, activate the 3'-hydroxyl group of ATP by lowering its pKa.
(2) The activated hydroxyl group makes a nucleophilic attack on alpha-phosphate group, leading to a pentavalent phosphate of the transtion-state.
(3) The transition-state of the alpha-phosphate is stabilized by Magnesium ion-A and Arg1029, whereas the leaving group, beta,gamma-phosphate groups, is stabilzed by the magnesium ion-B, which is bound to Asp440, Asp396 and mainchain carbonyl group of Ile397, as well as by Arg484 and Lys1065.

Created Updated
2004-04-12 2009-02-26