کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2830250 1163371 2008 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Species-specific inhibition of Giardia lamblia triosephosphate isomerase by localized perturbation of the homodimer
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Species-specific inhibition of Giardia lamblia triosephosphate isomerase by localized perturbation of the homodimer
چکیده انگلیسی

Giardia lamblia depends on glycolysis to obtain ATP, highlighting the suitability of glycolytic enzymes as targets for drug design. We studied triosephosphate isomerase from G. lamblia (GlTIM) as a potential species-specific drug target. Cysteine-reactive agents were used as probes, in order to test those regions near to cysteine residues as targets to perturb enzyme structure and activity. Methyl methanethiosulfonate (MMTS) derivatized three of the five Cys per subunit of dimeric GlTIM and induced 50% of inactivation. The 2-carboxyethyl methanethiosulfonate (MTSCE) modified four Cys and induced 97% of inactivation. Inactivation by MMTS or MTSCE did not affect secondary structure, nor induce dimer dissociation; however, Cys modification decreased thermal stability of enzyme. Inactivation and dissociation of the dimer to stable monomers were reached when four Cys were derivatized by 5,5′-dithio-bis(2-nitrobenzoic acid) (DTNB). The effects of DTNB were completely abolished when GlTIM was first treated with MMTS. The effect of thiol reagents on human TIM was also assayed; it is 180-fold less sensitive than GlTIM. Collectively, the data illustrate GlTIM as a good target for drug design.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Biochemical Parasitology - Volume 157, Issue 2, February 2008, Pages 179–186
نویسندگان
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