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

Kira S. Makarova, Nick V. Grishin

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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 β-sheet arrangement and packing of the surrounding α-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 β-sheet for substrate binding.

Original languageEnglish (US)
Pages (from-to)2537-2540
Number of pages4
JournalProtein Science
Volume8
Issue number11
DOIs
StatePublished - 1999

Keywords

  • Complex
  • Core I proxein
  • Cytochrome bc
  • Metalloenzymes
  • Mitochondrial processing peptidase
  • Molecular evolution
  • Thermolysin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Fingerprint Dive into the research topics of 'Thermolysin and mitochondrial processing peptidase: How far structure- functional convergence goes'. Together they form a unique fingerprint.

Cite this