کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2830136 1163358 2008 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Molecular cloning, expression, characterization and mutation of Plasmodium falciparum guanylate kinase
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Molecular cloning, expression, characterization and mutation of Plasmodium falciparum guanylate kinase
چکیده انگلیسی

The present work describes cloning, expression, purification, characterization, and mutation of Plasmodium falciparum guanylate kinase (PlasmoDB ID PFI1420w). Amino-acid sequence alignment revealed important differences especially in K42-V51, Y73-A77, and F100-L110, which include residues important for kinase activity, and at helix 3, which is important for domain movements. The catalytic efficiency for dGMP was 22-fold lower than that for GMP, whose value is the lowest among known guanylate kinases. dGMP was found to a competitive inhibitor for GMP with Ki = 0.148 mM and a mixed-type inhibitor with regard to ATP with measured Ki = 0.4 mM. The specificity constant (Kcat/Km) of the four examined mutants varied for natural substrate GMP/dGMP, indicating the involvement of different mechanisms in substrate recognition and subsequent loop-domain movement. These results show that P. falciparum guanylate kinase is structurally and biochemically distinct from other guanylate kinases and could be a possible target in drug development.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Biochemical Parasitology - Volume 159, Issue 2, June 2008, Pages 130–133
نویسندگان
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