Trypanosomatid phosphoglycerate mutases have multiple conformational and oligomeric states

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 monomeri...

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Main Authors:	Blackburn, Elizabeth A., Ahmad Fuad, Fazia Adyani, Morgan, Hugh P., Nowicki, Matthew W., Wear, Martin A., Michels, Paul A.M., Fothergill-Gilmore, Linda A., Walkinshaw, Malcolm D.
Format:	Article
Language:	English
Published:	ELSEVIER 2014
Subjects:	Q Science (General)
Online Access:	http://irep.iium.edu.my/45465/ http://irep.iium.edu.my/45465/ http://irep.iium.edu.my/45465/ http://irep.iium.edu.my/45465/1/%2BBlackburn_2014_BBRC.pdf

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recordtype	eprints
spelling	iium-454652015-11-02T03:42:16Z http://irep.iium.edu.my/45465/ Trypanosomatid phosphoglycerate mutases have multiple conformational and oligomeric states Blackburn, Elizabeth A. Ahmad Fuad, Fazia Adyani Morgan, Hugh P. Nowicki, Matthew W. Wear, Martin A. Michels, Paul A.M. Fothergill-Gilmore, Linda A. Walkinshaw, Malcolm D. Q Science (General) 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. ELSEVIER 2014 Article PeerReviewed application/pdf en http://irep.iium.edu.my/45465/1/%2BBlackburn_2014_BBRC.pdf 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 http://www.journals.elsevier.com/biochemical-and-biophysical-research-communications/ http://dx.doi.org/10.1016/j.bbrc.2014.06.113
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English
topic	Q Science (General)
spellingShingle	Q Science (General) Blackburn, Elizabeth A. Ahmad Fuad, Fazia Adyani Morgan, Hugh P. Nowicki, Matthew W. Wear, Martin A. Michels, Paul A.M. Fothergill-Gilmore, Linda A. Walkinshaw, Malcolm D. Trypanosomatid phosphoglycerate mutases have multiple conformational and oligomeric states
description	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.
format	Article
author	Blackburn, Elizabeth A. Ahmad Fuad, Fazia Adyani Morgan, Hugh P. Nowicki, Matthew W. Wear, Martin A. Michels, Paul A.M. Fothergill-Gilmore, Linda A. Walkinshaw, Malcolm D.
author_facet	Blackburn, Elizabeth A. Ahmad Fuad, Fazia Adyani Morgan, Hugh P. Nowicki, Matthew W. Wear, Martin A. Michels, Paul A.M. Fothergill-Gilmore, Linda A. Walkinshaw, Malcolm D.
author_sort	Blackburn, Elizabeth A.
title	Trypanosomatid phosphoglycerate mutases have multiple conformational and oligomeric states
title_short	Trypanosomatid phosphoglycerate mutases have multiple conformational and oligomeric states
title_full	Trypanosomatid phosphoglycerate mutases have multiple conformational and oligomeric states
title_fullStr	Trypanosomatid phosphoglycerate mutases have multiple conformational and oligomeric states
title_full_unstemmed	Trypanosomatid phosphoglycerate mutases have multiple conformational and oligomeric states
title_sort	trypanosomatid phosphoglycerate mutases have multiple conformational and oligomeric states
publisher	ELSEVIER
publishDate	2014
url	http://irep.iium.edu.my/45465/ http://irep.iium.edu.my/45465/ http://irep.iium.edu.my/45465/ http://irep.iium.edu.my/45465/1/%2BBlackburn_2014_BBRC.pdf
first_indexed	2023-09-18T21:04:42Z
last_indexed	2023-09-18T21:04:42Z
_version_	1777410855943536640

Trypanosomatid phosphoglycerate mutases have multiple conformational and oligomeric states

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