1p49 | pdb_00001p49
Structure of Human Placental Estrone/DHEA Sulfatase
Structural highlights
Disease[STS_HUMAN] Defects in STS are the cause of ichthyosis X-linked (IXL) [MIM:308100]. Ichthyosis X-linked is a keratinization disorder manifesting with mild erythroderma and generalized exfoliation of the skin within a few weeks after birth. Affected boys later develop large, polygonal, dark brown scales, especially on the neck, extremities, trunk, and buttocks.[1] [2] [3] [4] Function[STS_HUMAN] Conversion of sulfated steroid precursors to estrogens during pregnancy. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedEstrone 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. 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[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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