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Mapping Free Energy Pathways for ATP Hydrolysis in the E. coli ABC Transporter HlyB by the String Method

HlyB functions as an adenosine triphosphate (ATP)-binding cassette (ABC) transporter that enables bacteria to secrete toxins at the expense of ATP hydrolysis. Our previous work, based on potential energy profiles from combined quantum mechanical and molecular mechanical (QM/MM) calculations, has sug...

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Detalles Bibliográficos
Autores principales: Zhou, Yan, Ojeda-May, Pedro, Nagaraju, Mulpuri, Kim, Bryant, Pu, Jingzhi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222333/
https://www.ncbi.nlm.nih.gov/pubmed/30332773
http://dx.doi.org/10.3390/molecules23102652
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author Zhou, Yan
Ojeda-May, Pedro
Nagaraju, Mulpuri
Kim, Bryant
Pu, Jingzhi
author_facet Zhou, Yan
Ojeda-May, Pedro
Nagaraju, Mulpuri
Kim, Bryant
Pu, Jingzhi
author_sort Zhou, Yan
collection PubMed
description HlyB functions as an adenosine triphosphate (ATP)-binding cassette (ABC) transporter that enables bacteria to secrete toxins at the expense of ATP hydrolysis. Our previous work, based on potential energy profiles from combined quantum mechanical and molecular mechanical (QM/MM) calculations, has suggested that the highly conserved H-loop His residue H662 in the nucleotide binding domain (NBD) of E. coli HlyB may catalyze the hydrolysis of ATP through proton relay. To further test this hypothesis when entropic contributions are taken into account, we obtained QM/MM minimum free energy paths (MFEPs) for the HlyB reaction, making use of the string method in collective variables. The free energy profiles along the MFEPs confirm the direct participation of H662 in catalysis. The MFEP simulations of HlyB also reveal an intimate coupling between the chemical steps and a local protein conformational change involving the signature-loop residue S607, which may serve a catalytic role similar to an Arg-finger motif in many ATPases and GTPases in stabilizing the phosphoryl-transfer transition state.
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spelling pubmed-62223332018-11-13 Mapping Free Energy Pathways for ATP Hydrolysis in the E. coli ABC Transporter HlyB by the String Method Zhou, Yan Ojeda-May, Pedro Nagaraju, Mulpuri Kim, Bryant Pu, Jingzhi Molecules Article HlyB functions as an adenosine triphosphate (ATP)-binding cassette (ABC) transporter that enables bacteria to secrete toxins at the expense of ATP hydrolysis. Our previous work, based on potential energy profiles from combined quantum mechanical and molecular mechanical (QM/MM) calculations, has suggested that the highly conserved H-loop His residue H662 in the nucleotide binding domain (NBD) of E. coli HlyB may catalyze the hydrolysis of ATP through proton relay. To further test this hypothesis when entropic contributions are taken into account, we obtained QM/MM minimum free energy paths (MFEPs) for the HlyB reaction, making use of the string method in collective variables. The free energy profiles along the MFEPs confirm the direct participation of H662 in catalysis. The MFEP simulations of HlyB also reveal an intimate coupling between the chemical steps and a local protein conformational change involving the signature-loop residue S607, which may serve a catalytic role similar to an Arg-finger motif in many ATPases and GTPases in stabilizing the phosphoryl-transfer transition state. MDPI 2018-10-16 /pmc/articles/PMC6222333/ /pubmed/30332773 http://dx.doi.org/10.3390/molecules23102652 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhou, Yan
Ojeda-May, Pedro
Nagaraju, Mulpuri
Kim, Bryant
Pu, Jingzhi
Mapping Free Energy Pathways for ATP Hydrolysis in the E. coli ABC Transporter HlyB by the String Method
title Mapping Free Energy Pathways for ATP Hydrolysis in the E. coli ABC Transporter HlyB by the String Method
title_full Mapping Free Energy Pathways for ATP Hydrolysis in the E. coli ABC Transporter HlyB by the String Method
title_fullStr Mapping Free Energy Pathways for ATP Hydrolysis in the E. coli ABC Transporter HlyB by the String Method
title_full_unstemmed Mapping Free Energy Pathways for ATP Hydrolysis in the E. coli ABC Transporter HlyB by the String Method
title_short Mapping Free Energy Pathways for ATP Hydrolysis in the E. coli ABC Transporter HlyB by the String Method
title_sort mapping free energy pathways for atp hydrolysis in the e. coli abc transporter hlyb by the string method
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222333/
https://www.ncbi.nlm.nih.gov/pubmed/30332773
http://dx.doi.org/10.3390/molecules23102652
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