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Trypanosomatid phosphoglycerate mutases have multiple conformational and oligomeric states

Blackburn, Elizabeth A. and Ahmad Fuad, Fazia Adyani and Morgan, Hugh P. and Nowicki, Matthew W. and Wear, Martin A. and Michels, Paul A.M. and Fothergill-Gilmore, Linda A. and Walkinshaw, Malcolm D. (2014) Trypanosomatid phosphoglycerate mutases have multiple conformational and oligomeric states. Biochemical and Biophysical Research Communications, 450. pp. 936-941. ISSN 0006-291X

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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.

Item Type: Article (Journal)
Additional Information: 7200/45465
Uncontrolled Keywords: Chemotherapeutic target, Cofactor-independent PGAM, Leishmania mexicana SEC-MALS, Trypanosomatidae
Subjects: Q Science > Q Science (General)
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button): Kulliyyah of Engineering > Department of Biotechnology Engineering
Depositing User: Dr Fazia Adyani Ahmad Fuad
Date Deposited: 02 Nov 2015 11:42
Last Modified: 02 Nov 2015 11:42
URI: http://irep.iium.edu.my/id/eprint/45465

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