Phosphoglycerate mutase from Trypanosoma brucei is hyperactivated by cobalt in vitro, but not in vivo

Production of ATP by the glycolytic pathway in the mammalian pathogenic stage of protists from the genus Trypanosoma is required for the survival of the parasites. Cofactor-independent phosphoglycerate mutase (iPGAM) is particularly attractive as a drug target because it shows no similarity to the...

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Main Author:	Ahmad Fuad, Fazia Adyani
Format:	Article
Language:	English
Published:	Royal Society of Chemistry 2011
Subjects:	Q Science (General)
Online Access:	http://irep.iium.edu.my/45464/ http://irep.iium.edu.my/45464/ http://irep.iium.edu.my/45464/1/%2BFuad_et_al._2011.pdf

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spelling	iium-454642015-11-02T00:09:41Z http://irep.iium.edu.my/45464/ Phosphoglycerate mutase from Trypanosoma brucei is hyperactivated by cobalt in vitro, but not in vivo Ahmad Fuad, Fazia Adyani Q Science (General) Production of ATP by the glycolytic pathway in the mammalian pathogenic stage of protists from the genus Trypanosoma is required for the survival of the parasites. Cofactor-independent phosphoglycerate mutase (iPGAM) is particularly attractive as a drug target because it shows no similarity to the corresponding enzyme in humans, and has also been genetically validated as a target by RNAi experiments. It has previously been shown that trypanosomatid iPGAMs require Co2+ to reach maximal activity, but the biologically relevant metal has remained unclear. In this paper the metal content in the cytosol of procyclic and bloodstream-form T. brucei (analysed by inductively coupled plasma-optical emission spectroscopy) shows that Mg2+, Zn2+ and Fe2+ were the most abundant, whereas Co2+ was below the limit of detection (o0.035 mM). The low concentration indicates that Co2+ is unlikely to be the biologically relevant metal, but that instead, Mg2+ and/or Zn2+ may assume this role. Results from metal analysis of purified Leishmania mexicana iPGAM by inductively coupled plasma-mass spectrometry also show high concentrations of Mg2+ and Zn2+, and are consistent with this proposal. Our data suggest that in vivo cellular conditions lacking Co2+ are unable to support the maximal activity of iPGAM, but instead maintain its activity at a relatively low level by using Mg2+ and/or Zn2+. The physiological significance of these observations is being pursued by structural, biochemical and biophysical studies. Royal Society of Chemistry 2011-10 Article PeerReviewed application/pdf en http://irep.iium.edu.my/45464/1/%2BFuad_et_al._2011.pdf Ahmad Fuad, Fazia Adyani (2011) Phosphoglycerate mutase from Trypanosoma brucei is hyperactivated by cobalt in vitro, but not in vivo. Metallomics, 3. pp. 1310-1317. ISSN 1756-5901(print), 1756-591X(online) http://www.rsc.org/journals-books-databases/about-journals/metallomics/
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) Ahmad Fuad, Fazia Adyani Phosphoglycerate mutase from Trypanosoma brucei is hyperactivated by cobalt in vitro, but not in vivo
description	Production of ATP by the glycolytic pathway in the mammalian pathogenic stage of protists from the genus Trypanosoma is required for the survival of the parasites. Cofactor-independent phosphoglycerate mutase (iPGAM) is particularly attractive as a drug target because it shows no similarity to the corresponding enzyme in humans, and has also been genetically validated as a target by RNAi experiments. It has previously been shown that trypanosomatid iPGAMs require Co2+ to reach maximal activity, but the biologically relevant metal has remained unclear. In this paper the metal content in the cytosol of procyclic and bloodstream-form T. brucei (analysed by inductively coupled plasma-optical emission spectroscopy) shows that Mg2+, Zn2+ and Fe2+ were the most abundant, whereas Co2+ was below the limit of detection (o0.035 mM). The low concentration indicates that Co2+ is unlikely to be the biologically relevant metal, but that instead, Mg2+ and/or Zn2+ may assume this role. Results from metal analysis of purified Leishmania mexicana iPGAM by inductively coupled plasma-mass spectrometry also show high concentrations of Mg2+ and Zn2+, and are consistent with this proposal. Our data suggest that in vivo cellular conditions lacking Co2+ are unable to support the maximal activity of iPGAM, but instead maintain its activity at a relatively low level by using Mg2+ and/or Zn2+. The physiological significance of these observations is being pursued by structural, biochemical and biophysical studies.
format	Article
author	Ahmad Fuad, Fazia Adyani
author_facet	Ahmad Fuad, Fazia Adyani
author_sort	Ahmad Fuad, Fazia Adyani
title	Phosphoglycerate mutase from Trypanosoma brucei is hyperactivated by cobalt in vitro, but not in vivo
title_short	Phosphoglycerate mutase from Trypanosoma brucei is hyperactivated by cobalt in vitro, but not in vivo
title_full	Phosphoglycerate mutase from Trypanosoma brucei is hyperactivated by cobalt in vitro, but not in vivo
title_fullStr	Phosphoglycerate mutase from Trypanosoma brucei is hyperactivated by cobalt in vitro, but not in vivo
title_full_unstemmed	Phosphoglycerate mutase from Trypanosoma brucei is hyperactivated by cobalt in vitro, but not in vivo
title_sort	phosphoglycerate mutase from trypanosoma brucei is hyperactivated by cobalt in vitro, but not in vivo
publisher	Royal Society of Chemistry
publishDate	2011
url	http://irep.iium.edu.my/45464/ http://irep.iium.edu.my/45464/ http://irep.iium.edu.my/45464/1/%2BFuad_et_al._2011.pdf
first_indexed	2023-09-18T21:04:42Z
last_indexed	2023-09-18T21:04:42Z
_version_	1777410855793590272

Phosphoglycerate mutase from Trypanosoma brucei is hyperactivated by cobalt in vitro, but not in vivo

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