Structure of human estrone sulfatase suggests functional roles of membrane association.
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.
Hernandez-Guzman
Francisco G
FG
Department of Structural Biology, Hauptman-Woodward Medical Research Institute, Buffalo, New York 14203, USA.
Higashiyama
Tadayoshi
T
Pangborn
Walter
W
Osawa
Yoshio
Y
Ghosh
Debashis
D
D000595:Amino Acid Sequence; D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004721:Endoplasmic Reticulum / Q000201:enzymology; D005260:Female; D006801:Humans; D007425:Intracellular Membranes / Q000201:enzymology*; D008854:Microscopy, Electron; D008861:Microsomes / Q000201:enzymology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013429:Sulfatases / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism* / Q000648:ultrastructure
D013429:Sulfatases; C020121:estrone sulfatase