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2BW7

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

Summary for 2BW7
Entry DOI10.2210/pdb2bw7/pdb
Related1WC0 1WC1 1WC3 1WC4 1WC5 1WC6
DescriptorADENYLATE CYCLASE, DIPHOSPHOMETHYLPHOSPHONIC ACID ADENOSYL ESTER, MAGNESIUM ION, ... (6 entities in total)
Functional Keywordslyase, adenylyl cyclase, camp signaling, catechol estrogen, inhibitor complex, oxidoreductase
Biological sourceSPIRULINA PLATENSIS
Total number of polymer chains4
Total formula weight99613.84
Authors
Steegborn, C.,Litvin, T.N.,Hess, K.C.,Capper, A.B.,Taussig, R.,Buck, J.,Levin, L.R.,Wu, H. (deposition date: 2005-07-12, release date: 2005-07-20, Last modification date: 2024-05-08)
Primary citationSteegborn, C.,Litvin, T.N.,Hess, K.C.,Capper, A.B.,Taussig, R.,Buck, J.,Levin, L.R.,Wu, H.
A Novel Mechanism for Adenylyl Cyclase Inhibition from the Crystal Structure of its Complex with Catechol Estrogen
J.Biol.Chem., 280:31754-, 2005
Cited by
PubMed Abstract: 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.
PubMed: 16002394
DOI: 10.1074/JBC.M507144200
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.3 Å)
Structure validation

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数据于2025-07-30公开中

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