title: Characterization and Inhibitor Screening of Plateau Zokor Lactate Dehydrogenase C4.
abstract: Lactate dehydrogenase C4 (LDH-C4) is considered to be a target protein for the development of contraceptives. In this work, the characterization of plateau zokor LDH-C4 and the screening of a series of N-substituted oxamic acids as inhibitors against zokor LDH-C4 were reported. The cDNA of zokor LDH-C gene was cloned and expressed in Escherichia coli, from which the protein was purified and further characterized. The protein was a tetramer (LDH-C4) and thermally stable up to 62 °C with a K m of 63.9 μM for pyruvate and with optimal pH values of 7.95 and 10.1 for the forward and backward reactions respectively. Virtual and in vitro screening against zokor LDH-C4 revealed eight N-substituted oxamic acids with IC50s ranging from 198 to 2513 μM, higher than that of oxamic acid (150 μM) and (ethylamino)(oxo)acetic acid (59 μM). The inhibition potencies of N-substituted oxamic acids tested are in the micromolar range, and the increase in the length of substituting chain seems not to increase inhibition potency.
authors.affiliation: College of Life Science and Technology, Southwest University for Nationalities, Chengdu, Sichuan, 610041, People's Republic of China. 341400255@qq.com.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: He
authors.affiliation: School of Laboratory Medicine, Chengdu Medical College, Chengdu, Sichuan, 610500, People's Republic of China.
authors.forename: Qinglian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: College of Life Science and Technology, Southwest University for Nationalities, Chengdu, Sichuan, 610041, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan, 610041, People's Republic of China.
authors.forename: Jinhu
authors.initials: J
authors.lastname: Ma
mesh_terms: D000818:Animals; D018076:DNA, Complementary / Q000096:biosynthesis; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism; D010072:Oxamic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D012377:Rodentia / Q000235:genetics
chemical_list: D018076:DNA, Complementary; D007527:Isoenzymes; D019344:Lactic Acid; D007770:L-Lactate Dehydrogenase; C409673:lactate dehydrogenase C4; D010072:Oxamic Acid
keywords: Inhibitor screening; LDH-C4; Myospalax baileyi