کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2829023 1162780 2009 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Comparative structural studies on Lys49-phospholipases A2 from Bothrops genus reveal their myotoxic site
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Comparative structural studies on Lys49-phospholipases A2 from Bothrops genus reveal their myotoxic site
چکیده انگلیسی

Phospholipases A2 (PLA2s) are membrane-associated enzymes that hydrolyze phospholipids at the sn-2 position, releasing lysophospholipids and free fatty acids. Phospholipase A2 homologues (Lys49-PLA2s) are highly myotoxic and cause extensive tissue damage despite not showing measurable catalytic activity. They are found in different snake venoms and represent one third of bothropic venom composition. The importance of these toxins during envenomation is related to the pronounced local myotoxic effect they induce since this effect is not neutralized by serum therapy. We present herein three structures of Lys49-PLA2s from Bothrops genus snake venom crystallized under the same conditions, two of which were grown in the presence of α-tocopherol (vitamin E). Comparative structural analysis of these and other Lys49-PLA2s showed two different patterns of oligomeric conformation that are related to the presence or absence of ligands in the hydrophobic channel. This work also confirms the biological dimer indicated by recent studies in which both C-termini are in the dimeric interface. In this configuration, we propose that the myotoxic site of these toxins is composed by the Lys 20, Lys115 and Arg118 residues. For the first time, a residue from the short-helix (Lys20) is suggested as a member of this site and the importance of Tyr119 residue to myotoxicity of bothropic Lys49-PLA2s is also discussed. These results support a complete hypothesis for these PLA2s myotoxic activity consistent with all findings on bothropic Lys49-PLA2s studied up to this moment, including crystallographic, bioinformatics, biochemical and biophysical data.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Structural Biology - Volume 167, Issue 2, August 2009, Pages 106–116
نویسندگان
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