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Search for Human Lactate Dehydrogenase A Inhibitors Using Structure-Based Modeling

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 str...

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Detalles Bibliográficos
Autores principales: Nilov, D. K., Prokhorova, E. A., Švedas, V. K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: A.I. Gordeyev 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463413/
https://www.ncbi.nlm.nih.gov/pubmed/26085945
Descripción
Sumario: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.