title: Search for Human Lactate Dehydrogenase A Inhibitors Using Structure-Based Modeling.
abstract: The human lactate dehydrogenase isoform A plays an important role in the anaerobic metabolism of tumour cells and therefore constitutes an attractive target in the oncology field. Full-atom models of lactate dehydrogenase A (in complex with NADH and in the apo form) have been generated to enable structure-based design of novel inhibitors competing with pyruvate and NADH. The structural criteria for the selection of potential inhibitors were established, and virtual screening of a library of low-molecular-weight compounds was performed. A potential inhibitor, STK381370, was identified whose docking pose was stabilized through additional interactions with the loop 96-111 providing for the transition from the open to the closed conformation.
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskie Gory 1, bldg. 40, 119991 Moscow, Russia ; Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Leninskie Gory 1, bldg. 73, 119991, Moscow, Russia.
authors.forename: D K
authors.initials: DK
authors.lastname: Nilov
authors.affiliation: Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Leninskie Gory 1, bldg. 73, 119991, Moscow, Russia.
authors.forename: E A
authors.initials: EA
authors.lastname: Prokhorova
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskie Gory 1, bldg. 40, 119991 Moscow, Russia ; Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Leninskie Gory 1, bldg. 73, 119991, Moscow, Russia.
authors.forename: V K
authors.initials: VK
authors.lastname: Švedas
keywords: docking; inhibitor; lactate dehydrogenase; molecular modeling