Solution NMR structure of the NlpC/P60 domain of lipoprotein Spr from Escherichia coli: structural evidence for a novel cysteine peptidase catalytic triad.

TitleSolution NMR structure of the NlpC/P60 domain of lipoprotein Spr from Escherichia coli: structural evidence for a novel cysteine peptidase catalytic triad.
Publication TypeJournal Article
Year of Publication2008
AuthorsAramini, JM, Rossi, P, Huang, YJ, Zhao, L, Jiang, M, Maglaqui, M, Xiao, R, Locke, J, Nair, R, Rost, B, Acton, TB, Inouye, M, Montelione, GT
JournalBiochemistry
Volume47
Issue37
Pagination9715-7
Date Published2008 Sep 16
ISSN1520-4995
KeywordsAmino Acid Sequence, Catalysis, Catalytic Domain, Cysteine, Cysteine Endopeptidases, Escherichia coli, Escherichia coli Proteins, Histidine, Hydrolases, Magnetic Resonance Spectroscopy, Models, Molecular, Molecular Sequence Data, Peptide Hydrolases, Protein Folding, Protein Structure, Tertiary, Solutions
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.

DOI10.1021/bi8010779
Alternate JournalBiochemistry
PubMed ID18715016
Grant ListU54-GM074958 / GM / NIGMS NIH HHS / United States