title: Cd(2+)-induced aggregation of Escherichia coli pyrophosphatase.
abstract: We report here that Escherichia coli pyrophosphatase aggregates in the presence of millimolar Cd(2+). This highly cooperative process was specific to both the metal ion and the protein and could be reversed fully by decreasing the Cd(2+) concentration. Aggregation was enhanced by Mg(2+), the natural cofactor of pyrophosphatase, and Mn(2+). Mutations at the intersubunit metal-binding site had no effect, whereas mutation at Glu139, which is part of the peripheral metal-binding site found in pyrophosphatase crystals near the contact region between two enzyme molecules, suppressed aggregation. These findings indicate that aggregation is affected by Cd(2+) binding to the peripheral metal-binding site, probably by strengthening intermolecular Trp149-Trp149' stacking interactions.
authors.affiliation: A. N. Belozersky Institute of Physico-Chemical Biology and School of Chemistry, Moscow State University, Moscow, Russia.
authors.forename: Yury V
authors.initials: YV
authors.lastname: Zimenkov
authors.forename: Anu
authors.initials: A
authors.lastname: Salminen
authors.forename: Irina S
authors.initials: IS
authors.lastname: Efimova
authors.forename: Reijo
authors.initials: R
authors.lastname: Lahti
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Baykov
mesh_terms: D001665:Binding Sites; D002104:Cadmium / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D008345:Manganese / Q000378:metabolism; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D011755:Pyrophosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D029968:Escherichia coli Proteins; D002104:Cadmium; D008345:Manganese; D011755:Pyrophosphatases; D008274:Magnesium