title: Protonation of the acidic residues in the transmembrane cation-binding sites of the ca(2+) pump.
abstract: The ionization states of the acidic residues around the Ca2+-binding sites of sarcoplasmic reticulum Ca2+ ATPase are studied by continuum electrostatic calculations and all-atom molecular dynamics simulations with explicit solvent and phospholipids. The two methods consistently indicate that Glu58 and Glu908 are protonated at neutral pH. The Ca2+ coordination and the H-bonds formed by the protonation of Glu58 and Glu908 are stable in an MD simulation, whereas the H-bonds are disrupted and the Ca2+ coordination geometry is severely altered in another simulation treating these residues unprotonated. The results clearly indicate that the H-bonds formed by protonation of Glu58 and Glu908 provide extra stability for the Ca2+-binding sites of Ca2+ ATPase.
authors.affiliation: Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sugita
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Miyashita
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Ikeguchi
authors.forename: Akinori
authors.initials: A
authors.lastname: Kidera
authors.forename: Chikashi
authors.initials: C
authors.lastname: Toyoshima
mesh_terms: D001665:Binding Sites; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000737:chemistry* / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D011487:Protein Conformation; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium