The 1.4 a crystal structure of kumamolysin: a thermostable serine-carboxyl-type proteinase

Structure. 2002 Jun;10(6):865-76. doi: 10.1016/s0969-2126(02)00772-4.

Abstract

Kumamolysin is a thermostable endopeptidase from Bacillus novosp. MN-32, exhibiting maximal proteolytic activity around pH 3. It belongs to the newly identified family of serine-carboxyl proteinases, which also includes CLN2, a human lysosomal homolog recently implicated in a fatal neurodegenerative disease. Kumamolysin and its complexes with two aldehyde inhibitors were crystallized, and their three-dimensional structures were solved and refined with X-ray data to 1.4 A resolution. As its Pseudomonas homolog, kumamolysin exhibits a Ser/Glu/Asp catalytic triad with particularly short interconnecting hydrogen bonds and an oxyanion hole enabling the reactive serine to attack substrate peptide bonds at quite acidic pH. An additional Glu/Trp pair, unique to kumamolysin, might further facilitate proton delocalization during nucleophilic attack, in particular at high temperature.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Aspartic Acid Endopeptidases / antagonists & inhibitors
  • Aspartic Acid Endopeptidases / chemistry*
  • Aspartic Acid Endopeptidases / genetics
  • Aspartic Acid Endopeptidases / metabolism
  • Bacillus / chemistry
  • Bacillus / genetics
  • Bacillus / metabolism
  • Binding Sites
  • Calcium / metabolism
  • Crystallography, X-Ray
  • Hydrogen-Ion Concentration
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Subtilisin / genetics
  • Tripeptidyl-Peptidase 1

Substances

  • Tripeptidyl-Peptidase 1
  • TPP1 protein, human
  • Subtilisin
  • Aspartic Acid Endopeptidases
  • kumamolysin
  • Calcium

Associated data

  • GENBANK/AB070740
  • PDB/1GT9
  • PDB/1GTG
  • PDB/1GTJ
  • PDB/1GTL