1cul

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

spinqualitylabelsall models 1cul, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1cul is a 3 chain structure with sequence from Bos taurus, Canis lupus familiaris and Rattus norvegicus. The October 2004 RCSB PDB Molecule of the Month feature on G Proteins by David S. Goodsell is 10.2210/rcsb_pdb/mom_2004_10. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 103, 3PO, CL, FOK, GSP, MES, MG Related: 1cs4 Activity: Adenylate cyclase, with EC number 4.6.1.1 Resources: FirstGlance, OCA, RCSB, PDBsum Function [ADCY5_CANFA] This is a membrane-bound, calcium-inhibitable adenylyl cyclase. [GNAS2_BOVIN] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(s) protein is involved in hormonal regulation of adenylate cyclase: it activates the cyclase in response to beta-adrenergic stimuli. [ADCY2_RAT] This is a membrane-bound, calmodulin-insensitive adenylyl cyclase. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Adenylyl cyclase Guanine nucleotide-binding protein

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