Thermolysin and mitochondrial processing peptidase: how far structure-functional convergence goes

Protein Sci. 1999 Nov;8(11):2537-40. doi: 10.1110/ps.8.11.2537.

Abstract

The structure-functional convergence between two Zn-dependent proteases, namely thermolysin and mitochondrial processing peptidase (MPP), is described. These two families of nonhomologous enzymes show not only functional convergence of several active site residues as in chymotrypsin and subtilisin, but also structural convergence of overall molecular architectures including the beta-sheet arrangement and packing of the surrounding alpha-helices. The major functionally important structural elements are present in both enzymes with different topological connections and often in reverse main-chain orientation, but display similar packing. The structural comparison helps to rationalize sequence "inversion" of the HEXXH thermolysin consensus present as HXXEH in MPP. The described structural convergence may be due to a limited number of alternatives to build a Zn-protease that utilizes hydrogen bonding between a substrate main chain and the enzyme beta-sheet for substrate binding.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Metalloendopeptidases / chemistry*
  • Metalloendopeptidases / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Protein Structure, Secondary
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Structure-Activity Relationship
  • Thermolysin / chemistry*
  • Thermolysin / metabolism*

Substances

  • Metalloendopeptidases
  • Thermolysin
  • mitochondrial processing peptidase