2bw7: Difference between revisions

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.

2BW7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Arthrospira_platensis Arthrospira platensis] with MG, CA, APC and ECS as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Adenylate_cyclase Adenylate cyclase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.6.1.1 4.6.1.1] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BW7 OCA].  

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