1cul

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{{STRUCTURE_1cul| PDB=1cul | SCENE= }}
{{STRUCTURE_1cul| PDB=1cul | SCENE= }}
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'''COMPLEX OF GS-ALPHA WITH THE CATALYTIC DOMAINS OF MAMMALIAN ADENYLYL CYCLASE: COMPLEX WITH 2',5'-DIDEOXY-ADENOSINE 3'-TRIPHOSPHATE AND MG'''
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===COMPLEX OF GS-ALPHA WITH THE CATALYTIC DOMAINS OF MAMMALIAN ADENYLYL CYCLASE: COMPLEX WITH 2',5'-DIDEOXY-ADENOSINE 3'-TRIPHOSPHATE AND MG===
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==Overview==
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P-site inhibitors are adenosine and adenine nucleotide analogues that inhibit adenylyl cyclase, the effector enzyme that catalyzes the synthesis of cyclic AMP from ATP. Some of these inhibitors may represent physiological regulators of adenylyl cyclase, and the most potent may ultimately serve as useful therapeutic agents. Described here are crystal structures of the catalytic core of adenylyl cyclase complexed with two such P-site inhibitors, 2'-deoxyadenosine 3'-monophosphate (2'-d-3'-AMP) and 2',5'-dideoxyadenosine 3'-triphosphate (2',5'-dd-3'-ATP). Both inhibitors bind in the active site yet exhibit non- or uncompetitive patterns of inhibition. While most P-site inhibitors require pyrophosphate (PP(i)) as a coinhibitor, 2',5'-dd-3'-ATP is a potent inhibitor by itself. The crystal structure reveals that this inhibitor exhibits two binding modes: one with the nucleoside moiety bound to the nucleoside binding pocket of the enzyme and the other with the beta and gamma phosphates bound to the pyrophosphate site of the 2'-d-3'-AMP.PP(i) complex. A single metal binding site is observed in the complex with 2'-d-3'-AMP, whereas two are observed in the complex with 2', 5'-dd-3'-ATP. Even though P-site inhibitors are typically 10 times more potent in the presence of Mn(2+), the electron density maps reveal no inherent preference of either metal site for Mn(2+) over Mg(2+). 2',5'-dd-3'-ATP binds to the catalytic core of adenylyl cyclase with a K(d) of 2.4 microM in the presence of Mg(2+) and 0.2 microM in the presence of Mn(2+). Pyrophosphate does not compete with 2',5'-dd-3'-ATP and enhances inhibition.
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(as it appears on PubMed at http://www.pubmed.gov), where 11087399 is the PubMed ID number.
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{{ABSTRACT_PUBMED_11087399}}
==About this Structure==
==About this Structure==
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[[Category: Lyase/lyase/signaling protein]]
[[Category: Lyase/lyase/signaling protein]]
[[Category: Signal transducing protein]]
[[Category: Signal transducing protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 13:07:32 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 21:23:35 2008''

Revision as of 18:23, 30 June 2008

Image:1cul.png

Template:STRUCTURE 1cul

COMPLEX OF GS-ALPHA WITH THE CATALYTIC DOMAINS OF MAMMALIAN ADENYLYL CYCLASE: COMPLEX WITH 2',5'-DIDEOXY-ADENOSINE 3'-TRIPHOSPHATE AND MG

Template:ABSTRACT PUBMED 11087399

About this Structure

1CUL is a Protein complex structure of sequences from Bos taurus, Canis lupus familiaris and Rattus norvegicus. Full crystallographic information is available from OCA.

Reference

Molecular basis for P-site inhibition of adenylyl cyclase., Tesmer JJ, Dessauer CW, Sunahara RK, Murray LD, Johnson RA, Gilman AG, Sprang SR, Biochemistry. 2000 Nov 28;39(47):14464-71. PMID:11087399

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