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.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
Amino Acid Sequence
-
Catalysis
-
Catalytic Domain / genetics
-
Cysteine / chemistry
-
Cysteine / genetics*
-
Cysteine Endopeptidases / chemistry*
-
Cysteine Endopeptidases / metabolism
-
Escherichia coli / enzymology*
-
Escherichia coli / metabolism
-
Escherichia coli Proteins / chemistry*
-
Escherichia coli Proteins / metabolism
-
Histidine / chemistry
-
Histidine / genetics
-
Hydrolases / chemistry*
-
Hydrolases / metabolism
-
Magnetic Resonance Spectroscopy
-
Models, Molecular
-
Molecular Sequence Data
-
Peptide Hydrolases / chemistry*
-
Peptide Hydrolases / metabolism
-
Protein Folding
-
Protein Structure, Tertiary
-
Solutions
Substances
-
Escherichia coli Proteins
-
Solutions
-
Histidine
-
Hydrolases
-
Peptide Hydrolases
-
Cysteine Endopeptidases
-
mepS protein, E coli
-
Cysteine