title: Structural basis for the substrate specificity of PepA from Streptococcus pneumoniae, a dodecameric tetrahedral protease.
abstract: Regulated cytosolic proteolysis is one of the key cellular processes ensuring proper functioning of a cell. M42 family proteases show a broad spectrum of substrate specificities, but the structural basis for such diversity of the substrate specificities is lagging behind biochemical data. Here we report the crystal structure of PepA from Streptococcus pneumoniae, a glutamyl aminopeptidase belonging to M42 family (SpPepA). We found that Arg-257 in the substrate binding pocket is strategically positioned so that Arg-257 can make electrostatic interactions with the acidic residue of a substrate at its N-terminus. Structural comparison of the substrate binding pocket of the M42 family proteases, along with the structure-based multiple sequence alignment, argues that the appropriate electrostatic interactions contribute to the selective substrate specificity of SpPepA.
authors.affiliation: Department of Molecular and Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, South Korea.
authors.forename: Doyoun
authors.initials: D
authors.lastname: Kim
authors.forename: Boi Hoa
authors.initials: BH
authors.lastname: San
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Moh
authors.forename: Hyejin
authors.initials: H
authors.lastname: Park
authors.forename: Dong Young
authors.initials: DY
authors.lastname: Kim
authors.forename: Sangho
authors.initials: S
authors.lastname: Lee
authors.forename: Kyeong Kyu
authors.initials: KK
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D001120:Arginine / Q000737:chemistry / Q000235:genetics; D001665:Binding Sites; D018360:Crystallography, X-Ray; D043384:Glutamyl Aminopeptidase / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics; D055672:Static Electricity; D013296:Streptococcus pneumoniae / Q000201:enzymology*; D013379:Substrate Specificity
chemical_list: D021122:Protein Subunits; D001120:Arginine; D043384:Glutamyl Aminopeptidase