Trypanosomatid phosphoglycerate mutases have multiple conformational and oligomeric states

Elizabeth A. Blackburn, Fazia A A Fuad, Hugh P. Morgan, Matthew W. Nowicki, Martin A. Wear, Paul A M Michels, Linda A. Fothergill-Gilmore, Malcolm D. Walkinshaw*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Three structurally distinct forms of phosphoglycerate mutase from the trypanosomatid parasite Leishmania mexicana were isolated by standard procedures of bacterial expression and purification. Analytical size-exclusion chromatography coupled to a multi-angle scattering detector detected two monomeric forms of differing hydrodynamic radii, as well as a dimeric form. Structural comparisons of holoenzyme and apoenzyme trypanosomatid cofactor-independent phosphoglycerate mutase (iPGAM) X-ray crystal structures show a large conformational change between the open (apoenzyme) and closed (holoenzyme) forms accounting for the different monomer hydrodynamic radii. Until now iPGAM from trypanosomatids was considered to be only monomeric, but results presented here show the appearance of a dimeric form. Taken together, these observations are important for the choice of screening strategies to identify inhibitors of iPGAM for parasite chemotherapy and highlight the need to select the most biologically or functionally relevant form of the purified enzyme.

Original languageEnglish
Pages (from-to)936-941
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume450
Issue number2
Early online date28 Jun 2014
DOIs
Publication statusPublished - 25 Jul 2014

Keywords

  • chemotherapeutic target
  • cofactor-independent PGAM
  • leishmania mexicana
  • SEC-MALS
  • trypanosomatidae

Fingerprint Dive into the research topics of 'Trypanosomatid phosphoglycerate mutases have multiple conformational and oligomeric states'. Together they form a unique fingerprint.

Cite this