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| | {{STRUCTURE_1cs4| PDB=1cs4 | SCENE= }} | | {{STRUCTURE_1cs4| PDB=1cs4 | SCENE= }} |
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| - | '''COMPLEX OF GS-ALPHA WITH THE CATALYTIC DOMAINS OF MAMMALIAN ADENYLYL CYCLASE: COMPLEX WITH 2'-DEOXY-ADENOSINE 3'-MONOPHOSPHATE, PYROPHOSPHATE AND MG'''
| + | ===COMPLEX OF GS-ALPHA WITH THE CATALYTIC DOMAINS OF MAMMALIAN ADENYLYL CYCLASE: COMPLEX WITH 2'-DEOXY-ADENOSINE 3'-MONOPHOSPHATE, PYROPHOSPHATE 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_11087399}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 11087399 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_11087399}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Lyase/hydrolase complex]] | | [[Category: Lyase/hydrolase complex]] |
| | [[Category: Signal transducing protein]] | | [[Category: Signal transducing protein]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 13:03:31 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 21:15:43 2008'' |
Revision as of 18:15, 30 June 2008
Template:STRUCTURE 1cs4
COMPLEX OF GS-ALPHA WITH THE CATALYTIC DOMAINS OF MAMMALIAN ADENYLYL CYCLASE: COMPLEX WITH 2'-DEOXY-ADENOSINE 3'-MONOPHOSPHATE, PYROPHOSPHATE AND MG
Template:ABSTRACT PUBMED 11087399
About this Structure
1CS4 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
Page seeded by OCA on Mon Jun 30 21:15:43 2008
