کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8961928 1646525 2018 26 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
NMR methods to dissect the molecular mechanisms of disease-related mutations (DRMs): Understanding how DRMs remodel functional free energy landscapes
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
NMR methods to dissect the molecular mechanisms of disease-related mutations (DRMs): Understanding how DRMs remodel functional free energy landscapes
چکیده انگلیسی
Elucidating the molecular mechanism of disease-related mutations (DRMs) is a critical first step towards understanding the etiology of genetic disorders. DRMs often modulate biological function by altering the free-energy landscape (FEL) of the protein associated with the mutated gene. FELs typically include ground, as well as excited, yet accessible and functionally relevant, states and DRMs may perturb both the thermodynamics and kinetics of the ground vs. excited and apo vs. holo transitions. NMR is ideally suited to map at atomic-resolution these DRM-induced FEL perturbations. Here, we discuss NMR methods that can elucidate how DRMs remodel regulatory FELs by focusing on a simple, but prototypical, four-state allosteric FEL model. The approaches include the CHEmical Shift Projection Analysis, NMR spin relaxation measurements, and NMR measurements of effector-binding thermodynamics and kinetics. Together, these complementary NMR measurements provide a valuable picture of how DRMs modulate distinct FEL attributes that are critical for dissecting the molecular mechanisms underlying pathological phenotypes.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Methods - Volume 148, 15 September 2018, Pages 19-27
نویسندگان
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