|
|
| Line 1: |
Line 1: |
| [[Image:2bw7.gif|left|200px]] | | {{Seed}} |
| | [[Image:2bw7.png|left|200px]] |
|
| |
|
| <!-- | | <!-- |
| Line 9: |
Line 10: |
| {{STRUCTURE_2bw7| PDB=2bw7 | SCENE= }} | | {{STRUCTURE_2bw7| PDB=2bw7 | SCENE= }} |
|
| |
|
| '''A NOVEL MECHANISM FOR ADENYLYL CYCLASE INHIBITION FROM THE CRYSTAL STRUCTURE OF ITS COMPLEX WITH CATECHOL ESTROGEN'''
| | ===A NOVEL MECHANISM FOR ADENYLYL CYCLASE INHIBITION FROM THE CRYSTAL STRUCTURE OF ITS COMPLEX WITH CATECHOL ESTROGEN=== |
|
| |
|
|
| |
|
| ==Overview==
| | <!-- |
| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_16002394}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 16002394 is the PubMed ID number. |
| | --> |
| | {{ABSTRACT_PUBMED_16002394}} |
|
| |
|
| ==About this Structure== | | ==About this Structure== |
| Line 36: |
Line 40: |
| [[Category: Inhibitor complex]] | | [[Category: Inhibitor complex]] |
| [[Category: Oxidoreductase]] | | [[Category: Oxidoreductase]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 20:53:22 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 15:34:12 2008'' |