tailieunhanh - Báo cáo khóa học: How calcium inhibits the magnesium-dependent enzyme human phosphoserine phosphatase

The structure of the Mg 2+ -dependent enzyme human phosphoserine phosphatase (HPSP) was exploited to examine the structural and functional role of the divalent cation in the active site of phosphatases. Most interesting is the biochemical observation that a Ca 2+ ion inhibits the activity of HPSP, even in the presence of added Mg 2+ .The sixfold coordinated Mg 2+ ion present in the active site of HPSP under normal physiological conditions, was replaced by a Ca 2+ ion by using a crystallization conditionwith high concentration of CaCl2(). . | Eur. J. Biochem. 271 3421-3427 2004 FEBS 2004 doi How calcium inhibits the magnesium-dependent enzyme human phosphoserine phosphatase Yves Peeraer1 Anja Rabijns1. Jean-Francois Collet2 Emile Van Schaftinaen2 and Camiel De Ranter1 1 Laboratory for Analytical Chemistry and Medicinal Physicochemistry Faculty of Pharmaceutical Sciences . Leuven Leuven Belgium 2Laboratory of Physiological Chemistry Christian de Duve Institute of Cellular Pathology Universite Catholique de Louvain Brussels Belgium The structure of the Mg2 -dependent enzyme human phosphoserine phosphatase HPSP was exploited to examine the structural and functional role of the divalent cation in the active site of phosphatases. Most interesting is the biochemical observation that a Ca2 ion inhibits the activity of HPSP even in the presence of added Mg2 . The sixfold coordinated Mg2 ion present in the active site of HPSP under normal physiological conditions was replaced by a Ca2 ion by using a crystallization condition with high concentration of CaCl2 m . The resulting HPSP structure now shows a sevenfold coordinated Ca2 ion in the active site that might explain the inhibitory effect of Ca2 on the enzyme. Indeed the Ca2 ion in the active site captures both side-chain oxygen atoms of the catalytic Asp20 as a ligand while a Mg2 ion ligates only one oxygen atom of this Asp residue. The bidentate character of Asp20 towards Ca2 hampers the nucleophilic attack of one of the Asp20 side chain oxygen atoms on the phosphorus atom of the substrate phosphoserine. Keywords calcium HAD superfamily magnesium-dependent enzymes phosphoserine phosphatase L-serine. Human phosphoserine phosphatase HPSP catalyses the last and irreversible step of the de novo biosynthesis of L-serine . the hydrolysis of phosphoserine leading to the formation of L-serine and inorganic phosphate Pi . HPSP is a member of the haloacid dehalogenase HAD superfamily of which the members are characterized by .