机构:[1]“Tsinghua-IBP Joint Research Group for Structural Biology”, Tsinghua University, Beijing 100084, China[2]National Laboratory of Biomacromolecules, Institute of Biophysics (IBP), Chinese Academy of Sciences, Beijing 100101, China[3]Department of Cardiology, The First Affiliated Hospital of Kunming Medical College, Kunming 650032, China内科科室心脏内科昆明医科大学附属第一医院
Pyrroline-5-carboxylate reductase (P5CR) is a universal housekeeping enzyme that catalyzes the reduction of Delta(1)-pyrrohne-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, mtracellular redox potential, and apoptosis. Here, we present the 2.8 angstrom resolution structure of the P5CR apo enzyme, its 3.1 angstrom 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 degrees C. The enzyme is implicated in oxidation of the anti-tumor drug thioproline. (c) 2006 Elsevier Ltd. All rights reserved.
基金:
This work was
supported by Project ‘‘973’’ (grant no. g1999075602),
Project ‘‘863’’ (grant no. 2002BA711A12) and the
NSFC (grant no. 30221003).
第一作者机构:[1]“Tsinghua-IBP Joint Research Group for Structural Biology”, Tsinghua University, Beijing 100084, China[3]Department of Cardiology, The First Affiliated Hospital of Kunming Medical College, Kunming 650032, China
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推荐引用方式(GB/T 7714):
Zhaohui Meng,Zhiyong Lou,Zhe Liu,et al.Crystal structure of human pyrroline-5-carboxylate reductase[J].JOURNAL OF MOLECULAR BIOLOGY.2006,359(5):1364-1377.doi:10.1016/j.jmb.2006.04.053.
APA:
Zhaohui Meng,Zhiyong Lou,Zhe Liu,Ming Li,Xiaodong Zhao...&Zihe Rao.(2006).Crystal structure of human pyrroline-5-carboxylate reductase.JOURNAL OF MOLECULAR BIOLOGY,359,(5)
MLA:
Zhaohui Meng,et al."Crystal structure of human pyrroline-5-carboxylate reductase".JOURNAL OF MOLECULAR BIOLOGY 359..5(2006):1364-1377