کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2189412 1096210 2006 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Crystal Structure of Human Pyrroline-5-carboxylate Reductase
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Crystal Structure of Human Pyrroline-5-carboxylate Reductase
چکیده انگلیسی

Pyrroline-5-carboxylate reductase (P5CR) is a universal housekeeping enzyme that catalyzes the reduction of Δ1-pyrroline-5-carboxylate (P5C) to proline using NAD(P)H as the cofactor. The enzymatic cycle between P5C and proline is very important for the regulation of amino acid metabolism, intracellular redox potential, and apoptosis. Here, we present the 2.8 Å resolution structure of the P5CR apo enzyme, its 3.1 Å resolution ternary complex with NAD(P)H and substrate-analog. The refined structures demonstrate a decameric architecture with five homodimer subunits and ten catalytic sites arranged around a peripheral circular groove. Mutagenesis and kinetic studies reveal the pivotal roles of the dinucleotide-binding Rossmann motif and residue Glu221 in the human enzyme. Human P5CR is thermostable and the crystals were grown at 37 °C. The enzyme is implicated in oxidation of the anti-tumor drug thioproline.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Biology - Volume 359, Issue 5, 23 June 2006, Pages 1364–1377
نویسندگان
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