Crystal structures and biochemical studies of human lysophosphatidic acid phosphatase type 6

作     者：Jun Li Yu Dong Xingru Lü Lu Wang Wei Peng Xuejun C.Zhang Zihe Rao 

作者机构：National Laboratory of BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of SciencesBeijing 100049China Structure Biology LaboratoryTsinghua UniversityBeijing 100084China Tianjin Key Laboratory of Protein ScienceCollege of Life SciencesNankai UniversityTianjin 300071China 

出 版 物：《Protein & Cell》 (蛋白质与细胞（英文版）)

年 卷 期：2013年第4卷第7期

页      面：548-561页

核心收录：

学科分类：0710[理学-生物学] 0831[工学-生物医学工程（可授工学、理学、医学学位）] 1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070303[理学-有机化学] 0703[理学-化学] 0836[工学-生物工程] 

基　　金：the Ministry of Science and Technology of China(973 Project)(Grant Nos.2011CB915501 and 2011CB910304) National Infectious disease Funding(Grant No.2012ZX10004701) 

主　　题：lysophosphatidic acid histidine acid phos-phatase crystal structure 

摘      要：Lysophosphatidic acid(LPA)is an important bioac-tive phospholipid involved in cell signaling through G-protein-coupled receptors *** is also involved in balancing the lipid composition inside the cell,and modulates the function of lipid rafts as an intermediate in phospholipid *** of its involvement in these important processes,LPA degradation needs to be regulated as precisely as its ***-tidic acid phosphatase type 6(ACP6)is an LPA-specifi c acid phosphatase that hydrolyzes LPA to monoacylglyc-erol(MAG)and ***,we report three crystal structures of human ACP6 in complex with malonate,L-(+)-tartrate and tris,*** analyses revealed that ACP6 possesses a highly conserved Rossmann-fold-like body domain as well as a less conserved cap *** vast hydrophobic substrate-binding pocket,which is located between those two domains,is suitable for ac-commodating LPA,and its shape is different from that of other histidine acid phosphatases,a fact that is consistent with the observed difference in substrate *** analysis of the binding of three molecules in the active site reveals the involvement of six conserved and crucial residues in binding of the LPA phosphate group and its *** structure also indicates a water-supplying channel for substrate *** structural data are consistent with the fact that the enzyme is active as a *** combination with additional mutagenesis and enzyme activity studies,our structural data provide important insights into substrate recognition and the mechanism for catalytic activity of ACP6.