|
KEGG pathways | MAP code | Pathways |
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MAP00230 | Purine metabolism |
UniProtKB:Accession Number | P30803 | P26769 |
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Entry name | ADCY5_CANFA | ADCY2_RAT |
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Activity | ATP = 3'',5''-cyclic AMP + diphosphate. | ATP = 3'',5''-cyclic AMP + diphosphate. |
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Subunit |
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|
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Subcellular location | Membrane, Multi-pass membrane protein. | Membrane, Multi-pass membrane protein. |
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Cofactor | Binds 2 magnesium ions per subunit. | Binds 2 magnesium ions per subunit (By similarity). |
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Compound table: links to PDB-related databases & PoSSuM |
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| Cofactors | Substrates | Products |
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KEGG-id | C00305 | C00002 | C00131 | C00575 | C00968 | C00013 |
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Compound | Magnesium | ATP | dATP | 3',5'-Cyclic AMP | 3',5'-Cyclic dAMP | Pyrophosphate |
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Type | divalent metal (Ca2+, Mg2+) | amine group,nucleotide | amine group,nucleotide | amine group,nucleotide | amine group,nucleotide | phosphate group/phosphate ion |
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ChEBI | 18420
| 15422
| 16284
| 17489
| 28074
| 29888
|
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PubChem | 888
| 5957
| 15993
| 6076
| 188955
| 21961011 1023
|
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| | | | | | | | | | | | | |
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1azsA |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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1cjkA |  |  |  |  |  |  |  | Analogue:_MG-_MN | Analogue:AGS | Unbound | Unbound | Unbound | Unbound |
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1cjtA |  |  |  |  |  |  |  | Analogue:_MG-_MN | Unbound | Analogue:DAD | Unbound | Unbound | Unbound |
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1cjuA |  |  |  |  |  |  |  | Bound:2x_MG | Unbound | Analogue:DAD | Unbound | Unbound | Unbound |
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1cjvA |  |  |  |  |  |  |  | Analogue:_MG-_ZN | Unbound | Analogue:DAD | Unbound | Unbound | Unbound |
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1cs4A |  |  |  |  |  |  |  | Bound:_MG | Unbound | Unbound | Unbound | Unbound | Bound:POP |
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1culA |  |  |  |  |  |  |  | Bound:2x_MG | Unbound | Unbound | Unbound | Unbound | Analogue:3PO |
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1tl7A |  |  |  |  |  |  |  | Analogue:2x_MN | Analogue:ONM | Unbound | Unbound | Unbound | Unbound |
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1u0hA |  |  |  |  |  |  |  | Bound:2x_MG | Analogue:ONM | Unbound | Unbound | Unbound | Unbound |
---|
2gvdA |  |  |  |  |  |  |  | Analogue:2x_MN | Analogue:128 | Unbound | Unbound | Unbound | Unbound |
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2gvzA |  |  |  |  |  |  |  | Analogue:2x_MN | Analogue:ONA | Unbound | Unbound | Unbound | Unbound |
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1ab8A |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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1ab8B |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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1azsB |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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1cjkB |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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1cjtB |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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1cjuB |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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1cjvB |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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1cs4B |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Analogue:101 | Unbound |
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1culB |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Analogue:103 | Unbound |
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1tl7B |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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1u0hB |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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2gvdB |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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2gvzB |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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References for Catalytic Mechanism | References | Sections | No. of steps in catalysis |
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[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] |
---|
PubMed ID | 1525824 |
---|
Journal | Cell |
---|
Year | 1992 |
---|
Volume | 70 |
---|
Pages | 869-72 |
---|
Authors | Tang WJ, Gilman AG |
---|
Title | Adenylyl cyclases. |
---|
[2] |
---|
PubMed ID | 8418825 |
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Journal | Adv Second Messenger Phosphoprotein Res |
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Year | 1993 |
---|
Volume | 27 |
---|
Pages | 109-62 |
---|
Authors | Danchin A |
---|
Title | Phylogeny of adenylyl cyclases. |
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[3] |
---|
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. |
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[4] |
---|
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. |
---|
[5] |
---|
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? |
---|
[6] |
---|
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] |
---|
PubMed ID | 9391039 |
---|
Journal | Proc Natl Acad Sci U S A |
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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. |
---|
[8] |
---|
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. |
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[9] |
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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. |
---|
[10] |
---|
Comments | X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 870-1081 OF COMPLEX WITH G(S)-ALPHA. |
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Medline ID | 98072190 |
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PubMed ID | 9417641 |
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Journal | Science |
---|
Year | 1997 |
---|
Volume | 278 |
---|
Pages | 1907-16 |
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Authors | Tesmer JJ, Sunahara RK, Gilman AG, Sprang SR |
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Title | Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gsalpha.GTPgammaS. |
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Related PDB | 1azs |
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Related UniProtKB | P26769,P30803 |
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[11] |
---|
PubMed ID | 9819210 |
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Journal | Biochemistry |
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Year | 1998 |
---|
Volume | 37 |
---|
Pages | 16183-91 |
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Authors | Mitterauer T, Hohenegger M, Tang WJ, Nanoff C, Freissmuth M |
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Title | The C2 catalytic domain of adenylyl cyclase contains the second metal ion (Mn2+) binding site. |
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[12] |
---|
PubMed ID | 9914249 |
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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. |
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[13] |
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PubMed ID | 9632695 |
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Journal | J Biol Chem |
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Year | 1998 |
---|
Volume | 273 |
---|
Pages | 16332-8 |
---|
Authors | Sunahara RK, Beuve A, Tesmer JJ, Sprang SR, Garbers DL, Gilman AG |
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Title | Exchange of substrate and inhibitor specificities between adenylyl and guanylyl cyclases. |
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[14] |
---|
PubMed ID | 9677392 |
---|
Journal | J Biol Chem |
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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. |
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[15] |
---|
PubMed ID | 9687563 |
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Journal | Mol Pharmacol |
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Year | 1998 |
---|
Volume | 54 |
---|
Pages | 231-40 |
---|
Authors | Tang WJ, Hurley JH |
---|
Title | Catalytic mechanism and regulation of mammalian adenylyl cyclases. |
---|
[16] |
---|
PubMed ID | 10600134 |
---|
Journal | Biochemistry |
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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. |
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[17] |
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PubMed ID | 10075642 |
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Journal | J Biol Chem |
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Year | 1999 |
---|
Volume | 274 |
---|
Pages | 7599-602 |
---|
Authors | Hurley JH |
---|
Title | Structure, mechanism, and regulation of mammalian adenylyl cyclase. |
---|
[18] |
---|
Comments | X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 870-1081 OF COMPLEX WITH G(S)-ALPHA. |
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Medline ID | 99357873 |
---|
PubMed ID | 10427002 |
---|
Journal | Science |
---|
Year | 1999 |
---|
Volume | 285 |
---|
Pages | 756-60 |
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Authors | Tesmer JJ, Sunahara RK, Johnson RA, Gosselin G, Gilman AG, Sprang SR |
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Title | Two-metal-Ion catalysis in adenylyl cyclase. |
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Related PDB | 1cjk,1cjt,1cju,1cjv |
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Related UniProtKB | P26769,P30803 |
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[19] |
---|
PubMed ID | 10354616 |
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Journal | Trends Pharmacol Sci |
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Year | 1999 |
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Volume | 20 |
---|
Pages | 205-10 |
---|
Authors | Dessauer CW, Tesmer JJ, Sprang SR, Gilman AG |
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Title | The interactions of adenylate cyclases with P-site inhibitors. |
---|
[20] |
---|
PubMed ID | 10101967 |
---|
Journal | Trends Pharmacol Sci |
---|
Year | 1999 |
---|
Volume | 20 |
---|
Pages | 66-73 |
---|
Authors | Simonds WF |
---|
Title | G protein regulation of adenylate cyclase. |
---|
[21] |
---|
Comments | X-ray crystallography |
---|
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 |
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[22] |
---|
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. |
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[23] |
---|
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. |
---|
[24] |
---|
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. |
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[25] |
---|
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. |
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[26] |
---|
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. |
---|
[27] |
---|
PubMed ID | 12019229 |
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Journal | Genetics |
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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. |
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[28] |
---|
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. |
---|
[29] |
---|
PubMed ID | 12065575 |
---|
Journal | J Biol Chem |
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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. |
---|
[30] |
---|
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. |
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[31] |
---|
PubMed ID | 11665600 |
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Journal | Methods Enzymol |
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Year | 2002 |
---|
Volume | 345 |
---|
Pages | 127-40 |
---|
Authors | Hatley ME, Gilman AG, Sunahara RK |
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Title | Expression, purification, and assay of cytosolic (catalytic) domains of membrane-bound mammalian adenylyl cyclases. |
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[32] |
---|
PubMed ID | 11665605 |
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Journal | Methods Enzymol |
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Year | 2002 |
---|
Volume | 345 |
---|
Pages | 198-206 |
---|
Authors | Tesmer JJ, Sunahara RK, Fancy DA, Gilman AG, Sprang SR |
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Title | Crystallization of complex between soluble domains of adenylyl cyclase and activated Gs alpha. |
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[33] |
---|
PubMed ID | 16766715 |
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Journal | Mol Pharmacol |
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Year | 2006 |
---|
Volume | 70 |
---|
Pages | 878-86 |
---|
Authors | Mou TC, Gille A, Suryanarayana S, Richter M, Seifert R, Sprang SR |
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Title | Broad specificity of mammalian adenylyl cyclase for interaction with 2',3'-substituted purine- and pyrimidine nucleotide inhibitors. |
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Related PDB | 1tl7,1u0h |
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[34] |
---|
PubMed ID | 15591060 |
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Journal | J Biol Chem |
---|
Year | 2005 |
---|
Volume | 280 |
---|
Pages | 7253-61 |
---|
Authors | Mou TC, Gille A, Fancy DA, Seifert R, Sprang SR |
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Title | Structural basis for the inhibition of mammalian membrane adenylyl cyclase by 2'(3')-O-(N-Methylanthraniloyl)-guanosine 5 '-triphosphate. |
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Related PDB | 2gvd,2gvz |
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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.
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created | updated |
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2004-04-12 | 2009-02-26 |
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