The morpheein model of allosterism: a remedial step for targeting virulent l-asparaginase

Drug Discov Today. 2017 May;22(5):814-822. doi: 10.1016/j.drudis.2016.10.004. Epub 2016 Oct 11.

Abstract

Allosterism has emerged as an innovative and significant mode of drug discovery. It facilitates the targeting of an allosteric site that is unique and more specific. A relatively new approach to allosteric regulation is the morpheein model, a concerted dissociative model that describes the equilibrium of alternate quaternary structure assemblies, whose architectures are dictated by alternate conformations in the dissociated state. It is involved in various biological phenomena, including enzyme regulation. One such enzyme is l-asparaginase, which is exploited by pathogenic microbes to cause infectious disease in humans. Thus, the morpheein model can be applied as a novel approach to the discovery of allosteric modulators that regulate l-asparaginase function to control virulence and serves as the basis for novel drug discovery research.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation
  • Animals
  • Asparaginase / chemistry*
  • Asparaginase / metabolism*
  • Drug Discovery
  • Humans
  • Models, Molecular*
  • Virulence Factors / chemistry
  • Virulence Factors / metabolism

Substances

  • Virulence Factors
  • Asparaginase