1J99

CRYSTAL STRUCTURE OF HUMAN DEHYDROEPIANDROSTERONE SULFOTRANSFERASE IN COMPLEX WITH SUBSTRATE

1J99 の概要

• エントリーDOI: 10.2210/pdb1j99/pdb
• 分子名称: ALCOHOL SULFOTRANSFERASE, IODIDE ION, MERCURY (II) IODIDE, ... (5 entities in total)
• 機能のキーワード: dehydroepiandosterone, sulfotransferase, dhea, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q06520
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36495.23

構造登録者

Rehse, P.H.,Zhou, M.,Lin, S.-X. (登録日: 2001-05-24, 公開日: 2002-05-24, 最終更新日: 2023-08-16)

主引用文献

Rehse, P.H.,Zhou, M.,Lin, S.X.
Crystal structure of human dehydroepiandrosterone sulphotransferase in complex with substrate.
Biochem.J., 364:165-171, 2002

PubMed Abstract: Dehydroepiandrosterone sulphotransferase (DHEA-ST) is an enzyme that converts dehydroepiandrosterone (DHEA), and some other steroids, into their sulphonated forms. The enzyme catalyses the sulphonation of DHEA on the 3alpha-oxygen, with 3'-phosphoadenosine-5'-phosphosulphate contributing the sulphate. The structure of human DHEA-ST in complex with its preferred substrate DHEA has been solved here to 1.99 A using molecular replacement with oestradiol sulphotransferase (37% sequence identity) as a model. Two alternative substrate-binding orientations have been identified. The primary, catalytic, orientation has the DHEA 3alpha-oxygen and the highly conserved catalytic histidine in nearly identical positions as are seen for the related oestradiol sulphotransferase. The substrate, however, shows rotations of up to 30 degrees, and there is a corresponding rearrangement of the protein loops contributing to the active site. This may also reflect the low identity between the two enzymes. The second orientation penetrates further into the active site and can form a potential hydrogen bond with the desulphonated cofactor 3',5'-phosphoadenosine (PAP). This second site contains more van der Waal interactions with hydrophobic residues than the catalytic site and may also reflect the substrate-inhibition site. The PAP position was obtained from the previously solved structure of DHEA-ST co-crystallized with PAP. This latter structure, due to the arrangement of loops within the active site and monomer interactions, cannot bind substrate. The results presented here describe details of substrate binding to DHEA-ST and the potential relationship to substrate inhibition.

PubMed: 11988089

実験手法

X-RAY DIFFRACTION (1.99 Å)