1p49

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1p49, resolution 2.60Å

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Structure of Human Placental Estrone/DHEA Sulfatase

Contents

Overview

Estrone sulfatase (ES; 562 amino acids), one of the key enzymes, responsible for maintaining high levels of estrogens in breast tumor, cells, is associated with the membrane of the endoplasmic reticulum (ER)., The structure of ES, purified from the microsomal fraction of human, placentas, has been determined at 2.60-A resolution by x-ray, crystallography. This structure shows a domain consisting of two, antiparallel alpha-helices that protrude from the roughly spherical, molecule, thereby giving the molecule a "mushroom-like" shape. These, highly hydrophobic helices, each about 40 A long, are capable of, traversing the membrane, thus presumably anchoring the functional domain, on the membrane surface facing the ER lumen. The location of the, transmembrane domain is such that the opening to the active site, buried, deep in a cavity of the "gill" of the "mushroom," rests near the membrane, surface, thereby suggesting a role of the lipid bilayer in catalysis. This, simple architecture could be a prototype utilized by the ER membrane in, dictating the form and the function of ER-resident enzymes.

Disease

Known diseases associated with this structure: Ichthyosis, X-linked OMIM:[308100], Placental steroid sulfatase deficiency OMIM:[308100]

About this Structure

1P49 is a Single protein structure of sequence from Homo sapiens with , , and as ligands. Active as Steryl-sulfatase, with EC number 3.1.6.2 Full crystallographic information is available from OCA.

Reference

Structure of human estrone sulfatase suggests functional roles of membrane association., Hernandez-Guzman FG, Higashiyama T, Pangborn W, Osawa Y, Ghosh D, J Biol Chem. 2003 Jun 20;278(25):22989-97. Epub 2003 Mar 25. PMID:12657638

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