2BW7

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

2BW7 の概要

• エントリーDOI: 10.2210/pdb2bw7/pdb
• 関連するPDBエントリー: 1WC0 1WC1 1WC3 1WC4 1WC5 1WC6
• 分子名称: ADENYLATE CYCLASE, DIPHOSPHOMETHYLPHOSPHONIC ACID ADENOSYL ESTER, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: lyase, adenylyl cyclase, camp signaling, catechol estrogen, inhibitor complex, oxidoreductase
• 由来する生物種: SPIRULINA PLATENSIS
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 99613.84

構造登録者

Steegborn, C.,Litvin, T.N.,Hess, K.C.,Capper, A.B.,Taussig, R.,Buck, J.,Levin, L.R.,Wu, H. (登録日: 2005-07-12, 公開日: 2005-07-20, 最終更新日: 2024-05-08)

主引用文献

Steegborn, 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

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

実験手法

X-RAY DIFFRACTION (2.3 Å)