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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
A.I. Gordeyev
2015
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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. |
format | Online Article Text |
id | pubmed-4463413 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | A.I. Gordeyev |
record_format | MEDLINE/PubMed |
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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