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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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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
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author Nilov, D. K.
Prokhorova, E. A.
Švedas, V. K.
author_facet Nilov, D. K.
Prokhorova, E. A.
Švedas, V. K.
author_sort Nilov, D. K.
collection PubMed
description 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.
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spelling pubmed-44634132015-06-17 Search for Human Lactate Dehydrogenase A Inhibitors Using Structure-Based Modeling Nilov, D. K. Prokhorova, E. A. Švedas, V. K. Acta Naturae Research Article 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. A.I. Gordeyev 2015 /pmc/articles/PMC4463413/ /pubmed/26085945 Text en Copyright ® 2015 Park-media Ltd. http://creativecommons.org/licenses/by/2.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Nilov, D. K.
Prokhorova, E. A.
Švedas, V. K.
Search for Human Lactate Dehydrogenase A Inhibitors Using Structure-Based Modeling
title Search for Human Lactate Dehydrogenase A Inhibitors Using Structure-Based Modeling
title_full Search for Human Lactate Dehydrogenase A Inhibitors Using Structure-Based Modeling
title_fullStr Search for Human Lactate Dehydrogenase A Inhibitors Using Structure-Based Modeling
title_full_unstemmed Search for Human Lactate Dehydrogenase A Inhibitors Using Structure-Based Modeling
title_short Search for Human Lactate Dehydrogenase A Inhibitors Using Structure-Based Modeling
title_sort search for human lactate dehydrogenase a inhibitors using structure-based modeling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463413/
https://www.ncbi.nlm.nih.gov/pubmed/26085945
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