1X8J

Crystal structure of retinol dehydratase in complex with androsterone and inactive cofactor PAP

1X8J の概要

• エントリーDOI: 10.2210/pdb1x8j/pdb
• 関連するPDBエントリー: 1FML 1X8K 1X8L
• 分子名称: retinol dehydratase, CALCIUM ION, ADENOSINE-3'-5'-DIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: sulfotransferase, dehydratase, steroid binding., transferase
• 由来する生物種: Spodoptera frugiperda (fall armyworm)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 84562.15

構造登録者

Pakhomova, S.,Buck, J.,Newcomer, M.E. (登録日: 2004-08-18, 公開日: 2005-02-08, 最終更新日: 2023-08-23)

主引用文献

Pakhomova, S.,Buck, J.,Newcomer, M.E.
The structures of the unique sulfotransferase retinol dehydratase with product and inhibitors provide insight into enzyme mechanism and inhibition.
Protein Sci., 14:176-182, 2005

PubMed Abstract: The structure of retinol dehydratase (DHR) from Spodoptera frugiperda, a member of the sulfotransferase superfamily, in complexes with the inactive form of the cofactor PAP 3'-phosphoadenosine 5'-phosphate (PAP) and (1) the product of the reaction with retinol anhydroretinol (AR), (2) the retinoid inhibitor all-trans-4-oxoretinol (OR), and (3) the potent steroid inhibitor androsterone (AND) have been determined and compared to the enzyme complex with PAP and retinol. The structures show that the geometry of the active-site amino acids is largely preserved in the various complexes. However, the beta-ionone rings of the retinoids are oriented differently with respect to side chains that have been shown to be important for the enzymatic reaction. In addition, the DHR:PAP:AND complex reveals a novel mode for steroid binding that contrasts significantly with that for steroid binding in other sulfotransferases. The molecule is displaced and rotated approximately 180 degrees along its length so that there is no acceptor hydroxyl in close proximity to the site of sulfate transfer. This observation explains why steroids are potent inhibitors of retinol dehydratase activity, rather than substrates for sulfonation. Most of the steroid-protein contacts are provided by the alpha-helical cap that distinguishes this member of the superfamily. This observation suggests that in addition to providing a chemical environment that promotes the dehydration of a sulfonated intermediate, the cap may also serve to minimize a promiscuous sulfotransferases activity.

PubMed: 15608121
DOI: 10.1110/ps.041061105

実験手法

X-RAY DIFFRACTION (2.35 Å)