Cargando…
Exploration of Catalytic Selectivity for Aminotransferase (BtrR) Based on Multiple Molecular Dynamics Simulations
The aminotransferase from Bacillus circulans (BtrR), which is involved in the biosynthesis of butirosin, catalyzes the pyridoxal phosphate (PLP)-dependent transamination reaction to convert valienone to β-valienamine (a new β-glycosidase inhibitor for the treatment of lysosomal storage diseases) wit...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429434/ https://www.ncbi.nlm.nih.gov/pubmed/30857183 http://dx.doi.org/10.3390/ijms20051188 |
_version_ | 1783405594450853888 |
---|---|
author | Liu, Ye Wan, Youzhong Zhu, Jingxuan Li, Muxin Yu, Zhengfei Han, Jiarui Zhang, Zuoming Han, Weiwei |
author_facet | Liu, Ye Wan, Youzhong Zhu, Jingxuan Li, Muxin Yu, Zhengfei Han, Jiarui Zhang, Zuoming Han, Weiwei |
author_sort | Liu, Ye |
collection | PubMed |
description | The aminotransferase from Bacillus circulans (BtrR), which is involved in the biosynthesis of butirosin, catalyzes the pyridoxal phosphate (PLP)-dependent transamination reaction to convert valienone to β-valienamine (a new β-glycosidase inhibitor for the treatment of lysosomal storage diseases) with an optical purity enantiomeric excess value. To explore the stereoselective mechanism of valienamine generated by BtrR, multiple molecular dynamics (MD) simulations were performed for the BtrR/PLP/valienamine and BtrR/PLP/β-valienamine complexes. The theoretical results showed that β-valienamine could make BtrR more stable and dense than valienamine. β-valienamine could increase the hydrogen bond probability and decrease the binding free energy between coenzyme PLP and BtrR by regulating the protein structure of BtrR, which was conducive to the catalytic reaction. β-valienamine maintained the formation of cation-p interactions between basic and aromatic amino acids in BtrR, thus enhancing its stability and catalytic activity. In addition, CAVER 3.0 analysis revealed that β-valienamine could make the tunnel of BtrR wider and straight, which was propitious to the removal of products from BtrR. Steered MD simulation results showed that valienamine interacted with more residues in the tunnel during dissociation compared with β-valienamine, resulting in the need for a stronger force to be acquired from BtrR. Taken together, BtrR was more inclined to catalyze the substrates to form β-valienamine, either from the point of view of the catalytic reaction or product removal. |
format | Online Article Text |
id | pubmed-6429434 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-64294342019-04-10 Exploration of Catalytic Selectivity for Aminotransferase (BtrR) Based on Multiple Molecular Dynamics Simulations Liu, Ye Wan, Youzhong Zhu, Jingxuan Li, Muxin Yu, Zhengfei Han, Jiarui Zhang, Zuoming Han, Weiwei Int J Mol Sci Article The aminotransferase from Bacillus circulans (BtrR), which is involved in the biosynthesis of butirosin, catalyzes the pyridoxal phosphate (PLP)-dependent transamination reaction to convert valienone to β-valienamine (a new β-glycosidase inhibitor for the treatment of lysosomal storage diseases) with an optical purity enantiomeric excess value. To explore the stereoselective mechanism of valienamine generated by BtrR, multiple molecular dynamics (MD) simulations were performed for the BtrR/PLP/valienamine and BtrR/PLP/β-valienamine complexes. The theoretical results showed that β-valienamine could make BtrR more stable and dense than valienamine. β-valienamine could increase the hydrogen bond probability and decrease the binding free energy between coenzyme PLP and BtrR by regulating the protein structure of BtrR, which was conducive to the catalytic reaction. β-valienamine maintained the formation of cation-p interactions between basic and aromatic amino acids in BtrR, thus enhancing its stability and catalytic activity. In addition, CAVER 3.0 analysis revealed that β-valienamine could make the tunnel of BtrR wider and straight, which was propitious to the removal of products from BtrR. Steered MD simulation results showed that valienamine interacted with more residues in the tunnel during dissociation compared with β-valienamine, resulting in the need for a stronger force to be acquired from BtrR. Taken together, BtrR was more inclined to catalyze the substrates to form β-valienamine, either from the point of view of the catalytic reaction or product removal. MDPI 2019-03-08 /pmc/articles/PMC6429434/ /pubmed/30857183 http://dx.doi.org/10.3390/ijms20051188 Text en © 2019 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 Liu, Ye Wan, Youzhong Zhu, Jingxuan Li, Muxin Yu, Zhengfei Han, Jiarui Zhang, Zuoming Han, Weiwei Exploration of Catalytic Selectivity for Aminotransferase (BtrR) Based on Multiple Molecular Dynamics Simulations |
title | Exploration of Catalytic Selectivity for Aminotransferase (BtrR) Based on Multiple Molecular Dynamics Simulations |
title_full | Exploration of Catalytic Selectivity for Aminotransferase (BtrR) Based on Multiple Molecular Dynamics Simulations |
title_fullStr | Exploration of Catalytic Selectivity for Aminotransferase (BtrR) Based on Multiple Molecular Dynamics Simulations |
title_full_unstemmed | Exploration of Catalytic Selectivity for Aminotransferase (BtrR) Based on Multiple Molecular Dynamics Simulations |
title_short | Exploration of Catalytic Selectivity for Aminotransferase (BtrR) Based on Multiple Molecular Dynamics Simulations |
title_sort | exploration of catalytic selectivity for aminotransferase (btrr) based on multiple molecular dynamics simulations |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429434/ https://www.ncbi.nlm.nih.gov/pubmed/30857183 http://dx.doi.org/10.3390/ijms20051188 |
work_keys_str_mv | AT liuye explorationofcatalyticselectivityforaminotransferasebtrrbasedonmultiplemoleculardynamicssimulations AT wanyouzhong explorationofcatalyticselectivityforaminotransferasebtrrbasedonmultiplemoleculardynamicssimulations AT zhujingxuan explorationofcatalyticselectivityforaminotransferasebtrrbasedonmultiplemoleculardynamicssimulations AT limuxin explorationofcatalyticselectivityforaminotransferasebtrrbasedonmultiplemoleculardynamicssimulations AT yuzhengfei explorationofcatalyticselectivityforaminotransferasebtrrbasedonmultiplemoleculardynamicssimulations AT hanjiarui explorationofcatalyticselectivityforaminotransferasebtrrbasedonmultiplemoleculardynamicssimulations AT zhangzuoming explorationofcatalyticselectivityforaminotransferasebtrrbasedonmultiplemoleculardynamicssimulations AT hanweiwei explorationofcatalyticselectivityforaminotransferasebtrrbasedonmultiplemoleculardynamicssimulations |