New structural insights provide a different angle on steroid sulfatase action

P A Foster; J W Mueller

doi:10.1016/j.jsbmb.2023.106353

New structural insights provide a different angle on steroid sulfatase action

P A Foster^*, J W Mueller^*

^*Corresponding author for this work

Metabolism and Systems Research

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Abstract

A central part of human sulfation pathways is the spatially and temporally controlled desulfation of biologically highly potent steroid hormones. The responsible enzyme - steroid sulfatase (STS) - is highly expressed in placenta and peripheral tissues, such as fat, colon, and the brain. The shape of this enzyme and its mechanism are probably unique in biochemistry. STS was believed to be a transmembrane protein, spanning the Golgi double-membrane by stem region formed by two extended internal alpha-helices. New crystallographic data however challenge this view. STS now is portraited as a trimeric membrane-associated complex. We discuss the impact of these results on STS function and sulfation pathways in general and we hypothesis that this new STS structural understanding suggests product inhibition to be a regulator of STS enzymatic activity.

Original language	English
Article number	106353
Journal	The Journal of Steroid Biochemistry and Molecular Biology
Volume	232
Early online date	17 Jun 2023
DOIs	https://doi.org/10.1016/j.jsbmb.2023.106353
Publication status	Published - Sept 2023

Keywords

Sulfation pathways
Steroid sulfatase
Membrane-associated
Trimer formation
Structural biology

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title = "New structural insights provide a different angle on steroid sulfatase action",

abstract = "A central part of human sulfation pathways is the spatially and temporally controlled desulfation of biologically highly potent steroid hormones. The responsible enzyme - steroid sulfatase (STS) - is highly expressed in placenta and peripheral tissues, such as fat, colon, and the brain. The shape of this enzyme and its mechanism are probably unique in biochemistry. STS was believed to be a transmembrane protein, spanning the Golgi double-membrane by stem region formed by two extended internal alpha-helices. New crystallographic data however challenge this view. STS now is portraited as a trimeric membrane-associated complex. We discuss the impact of these results on STS function and sulfation pathways in general and we hypothesis that this new STS structural understanding suggests product inhibition to be a regulator of STS enzymatic activity.",

keywords = "Sulfation pathways, Steroid sulfatase, Membrane-associated, Trimer formation, Structural biology",

author = "Foster, {P A} and Mueller, {J W}",

year = "2023",

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language = "English",

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journal = "The Journal of Steroid Biochemistry and Molecular Biology",

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T1 - New structural insights provide a different angle on steroid sulfatase action

AU - Foster, P A

AU - Mueller, J W

PY - 2023/9

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AB - A central part of human sulfation pathways is the spatially and temporally controlled desulfation of biologically highly potent steroid hormones. The responsible enzyme - steroid sulfatase (STS) - is highly expressed in placenta and peripheral tissues, such as fat, colon, and the brain. The shape of this enzyme and its mechanism are probably unique in biochemistry. STS was believed to be a transmembrane protein, spanning the Golgi double-membrane by stem region formed by two extended internal alpha-helices. New crystallographic data however challenge this view. STS now is portraited as a trimeric membrane-associated complex. We discuss the impact of these results on STS function and sulfation pathways in general and we hypothesis that this new STS structural understanding suggests product inhibition to be a regulator of STS enzymatic activity.

KW - Sulfation pathways

KW - Steroid sulfatase

KW - Membrane-associated

KW - Trimer formation

KW - Structural biology

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DO - 10.1016/j.jsbmb.2023.106353

M3 - Article

C2 - 37331434

SN - 0960-0760

VL - 232

JO - The Journal of Steroid Biochemistry and Molecular Biology

JF - The Journal of Steroid Biochemistry and Molecular Biology

M1 - 106353

ER -

New structural insights provide a different angle on steroid sulfatase action

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