8EG3

Structure of human placental steroid (estrone/DHEA) sulfatase at 2.0 angstrom resolution

8EG3 の概要

• エントリーDOI: 10.2210/pdb8eg3/pdb
• 分子名称: Steryl-sulfatase, CALCIUM ION, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: steroid, sulfatase, sex steroid biosynthesis, er membrane-bound enzyme, hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 66809.30

構造登録者

Ghosh, D. (登録日: 2022-09-10, 公開日: 2022-12-07, 最終更新日: 2023-10-25)

主引用文献

Ghosh, D.
Structure of human placental steroid sulfatase at 2.0 angstrom resolution: Catalysis, quaternary association, and a secondary ligand site.
J.Steroid Biochem.Mol.Biol., 227:106228-106228, 2022

PubMed Abstract: Human placental estrone (E1)/dehydroepiandrosterone (DHEA) sulfatase (human placental steroid sulfatase; hSTS) is an integral membrane protein of the endoplasmic reticulum. This Ca-dependent enzyme catalyzes the hydrolysis of sulfate esters of E1 and DHEA to yield the respective unconjugated steroids, which then act as precursors for the biosynthesis of 17β-estradiol (E2) and dihydrotestosterone (DHT), respectively, the most potent forms of estrogens and androgens. hSTS is a key enzyme for the local production of E2 and DHT in the breast and the prostate. The enzyme is known to be responsible for maintaining high levels of estrogens in the breast tumor cells. The crystal structure of hSTS purified from human placenta has previously been reported at 2.6 Å resolution. Here we present the structure of hSTS determined at the superior 2.0 Å resolution bringing new clarity to the atomic architecture of the active site. The molecular basis of catalysis and steroid-protein interaction are revisited in light of the new data. We also reexamine the enzyme's quaternary association and its implication on the membrane integration. A secondary ligand binding pocket at the intermolecular interface and adjacent to the active site access channel, buried into the gill of the mushroom-shaped molecule, has been identified. Its role as well as that of a phosphate ion bound to an exposed histidine side chain are examined from the structure-function perspective. Higher resolution data also aids in the tracing of an important loop missing in the previous structure.

PubMed: 36427797
DOI: 10.1016/j.jsbmb.2022.106228

実験手法

X-RAY DIFFRACTION (2.04 Å)