title: Solution NMR structure of the NlpC/P60 domain of lipoprotein Spr from Escherichia coli: structural evidence for a novel cysteine peptidase catalytic triad.
abstract: Escherichia coli Spr is a membrane-anchored cell wall hydrolase. The solution NMR structure of the C-terminal NlpC/P60 domain of E. coli Spr described here reveals that the protein adopts a papain-like alpha+beta fold and identifies a substrate-binding cleft featuring several highly conserved residues. The active site features a novel Cys-His-His catalytic triad that appears to be a unique structural signature of this cysteine peptidase family. Moreover, the relative orientation of these catalytic residues is similar to that observed in the analogous Ser-His-His triad, a variant of the classic Ser-His-Asp charge relay system, suggesting the convergent evolution of a catalytic mechanism in quite distinct peptidase families.
authors: Center for Advanced Biotechnology and Medicine, Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA. jma@cabm.rutgers.edu
authors: James M
authors: JM
authors: Aramini
authors: Paolo
authors: P
authors: Rossi
authors: Yuanpeng J
authors: YJ
authors: Huang
authors: Li
authors: L
authors: Zhao
authors: Mei
authors: M
authors: Jiang
authors: Melissa
authors: M
authors: Maglaqui
authors: Rong
authors: R
authors: Xiao
authors: Jessica
authors: J
authors: Locke
authors: Rajesh
authors: R
authors: Nair
authors: Burkhard
authors: B
authors: Rost
authors: Thomas B
authors: TB
authors: Acton
authors: Masayori
authors: M
authors: Inouye
authors: Gaetano T
authors: GT
authors: Montelione
mesh_terms: D000595:Amino Acid Sequence; D002384:Catalysis; D020134:Catalytic Domain / Q000235:genetics; D003545:Cysteine / Q000737:chemistry / Q000235:genetics*; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D006639:Histidine / Q000737:chemistry / Q000235:genetics; D006867:Hydrolases / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000737:chemistry* / Q000378:metabolism; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012996:Solutions
chemical_list: D029968:Escherichia coli Proteins; D012996:Solutions; D006639:Histidine; D006867:Hydrolases; D010447:Peptide Hydrolases; D003546:Cysteine Endopeptidases; C532221:mepS protein, E coli; D003545:Cysteine