کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2048901 1074106 2010 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
MDM4 binds ligands via a mechanism in which disordered regions become structured
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک دانش گیاه شناسی
پیش نمایش صفحه اول مقاله
MDM4 binds ligands via a mechanism in which disordered regions become structured
چکیده انگلیسی

MDM2 and MDM4 are proteins involved in regulating the tumour suppressor p53. MDM2/4 and p53 interact through their N-terminal domains and disrupting this interaction is a potential anticancer strategy. The MDM2–p53 interaction is structurally and biophysically well characterised, whereas equivalent studies on MDM4 are hampered by aggregation of the protein. Here we present the NMR characterization of MDM4 (14-111) both free and in complexes with peptide and small-molecule ligands. MDM4 is more dynamic in its apo state than is MDM2, with parts of the protein being unstructured. These regions become structured upon binding of a ligand. MDM4 appears to bind its ligand through conformational selection and/or an induced fit mechanism; this might influence rational design of MDM4 inhibitors.Structured summaryMINT-7896835: p53 (uniprotkb:P04637) and MDM4 (uniprotkb:O15151) bind (MI:0407) by isothermal titration calorimetry (MI:0065)MINT-7896820: p53 (uniprotkb:P04637) and MDM4 (uniprotkb:O15151) bind (MI:0407) by nuclear magnetic resonance (MI:0077)

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: FEBS Letters - Volume 584, Issue 14, 16 July 2010, Pages 3035–3041
نویسندگان
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