2bw7

A novel mechanism for adenylyl cyclase inhibition from the crystal structure of its complex with catechol estrogen

spinqualitylabelsall models 2bw7, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2bw7 is a 4 chain structure with sequence from Artpt. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: APC, CA, ECS, MG Related: 1wc0, 1wc1, 1wc3, 1wc4, 1wc5, 1wc6 Activity: Adenylate cyclase, with EC number 4.6.1.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 Catechol estrogens are steroid metabolites that elicit physiological responses through binding to a variety of cellular targets. We show here that catechol estrogens directly inhibit soluble adenylyl cyclases and the abundant trans-membrane adenylyl cyclases. Catechol estrogen inhibition is non-competitive with respect to the substrate ATP, and we solved the crystal structure of a catechol estrogen bound to a soluble adenylyl cyclase from Spirulina platensis in complex with a substrate analog. The catechol estrogen is bound to a newly identified, conserved hydrophobic patch near the active center but distinct from the ATP-binding cleft. Inhibitor binding leads to a chelating interaction between the catechol estrogen hydroxyl groups and the catalytic magnesium ion, distorting the active site and trapping the enzyme substrate complex in a non-productive conformation. This novel inhibition mechanism likely applies to other adenylyl cyclase inhibitors, and the identified ligand-binding site has important implications for the development of specific adenylyl cyclase inhibitors. A novel mechanism for adenylyl cyclase inhibition from the crystal structure of its complex with catechol estrogen.,Steegborn C, Litvin TN, Hess KC, Capper AB, Taussig R, Buck J, Levin LR, Wu H J Biol Chem. 2005 Sep 9;280(36):31754-9. Epub 2005 Jul 7. PMID:16002394 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also 3D Adenylyl cyclase 3D structures

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