Theoretical prediction and experimental verification on enantioselectivity of haloacid dehalogenase l-DEX YL with chloropropionate

Kondo, Hirotaka; Fujimoto, Kazuhiro; Tanaka, Shigenori; Deki, Hiroyuki; Nakamura, Takashi

doi:10.1016/j.cplett.2015.01.053

Cited by 9 publications

(8 citation statements)

References 33 publications

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“…The 2-haloacid dehalogenases show typical stereoselectivity; however, little is known about the stereoselective mechanism. The enantioselective mechanism of L-DEX has been studied using quantum mechanics/molecular mechanics (QM/MM) and fragment molecular orbital calculation (Kondo et al, 2015;Adamu et al, 2019), which have confirmed that the high activation energy barrier prevents this enzyme from acting on the D-substrate. However, it is still unclear how selectivity of enzymes on chiral substrates is regulated.…”

Section: Discussion and Prospectsmentioning

confidence: 91%

Mini Review: Advances in 2-Haloacid Dehalogenases

et al. 2021

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The 2-haloacid dehalogenases (EC 3.8.1.X) are industrially important enzymes that catalyze the cleavage of carbon–halogen bonds in 2-haloalkanoic acids, releasing halogen ions and producing corresponding 2-hydroxyl acids. These enzymes are of particular interest in environmental remediation and environmentally friendly synthesis of optically pure chiral compounds due to their ability to degrade a wide range of halogenated compounds with astonishing efficiency for enantiomer resolution. The 2-haloacid dehalogenases have been extensively studied with regard to their biochemical characterization, protein crystal structures, and catalytic mechanisms. This paper comprehensively reviews the source of isolation, classification, protein structures, reaction mechanisms, biochemical properties, and application of 2-haloacid dehalogenases; current trends and avenues for further development have also been included.

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Section: Discussion and Prospectsmentioning

confidence: 91%

Mini Review: Advances in 2-Haloacid Dehalogenases

et al. 2021

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“…Considering that the interaction energies were accurately calculated in the second step at the MP2/6–31G* level and the widespread opinion that in most cases the 3–21G basis set provides geometries that are as good as the more expensive 4–31G and 6–31G sets, the chosen solution is the consensus of the computing time and accuracy. Recently, a similar calculation protocol (ONIOM and next FMO) was applied to optimize the fragment containing 105 atoms using the semi‐empirical PM3 method …”

Section: Methodsmentioning

confidence: 99%

“…QM/MM methods are especially suitable for studying large biological systems and, to date, have provided molecular‐level insights into many processes, such as the photosensitivity of visual pigments, enzyme catalysis, drug recognition by receptors, and cytotoxic activity mechanisms . It must be stressed that relatively few ONIOM studies have focused on one of the most important groups of biological targets, a family of G protein‐coupled receptors (GPCRs).…”

Section: Introductionmentioning

confidence: 99%

“…To the best of our knowledge, this is the first study to combine two powerful tools, that is, ONIOM and FMO, to analyze the structure–activity relationships (SARs) in the GPCR modulators. A similar methodology was recently successfully applied to investigate the enzymatic reaction . In addition, the results were compared to those obtained using the automated (classical) docking method.…”

Section: Introductionmentioning

confidence: 99%

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ONIOM and FMO‐EDA study of metabotropic glutamate receptor 1: Quantum insights into the allosteric binding site

Śliwa

Kurczab

Bojarski

2018

Int J of Quantum Chemistry

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The crystal structure of metabotropic glutamate receptor 1 (mGluR1) complexed with 4‐fluoro‐N‐(4‐(6‐(isopropylamino)pyrimidin‐4‐yl)thiazol‐2‐yl)‐N‐methylbenzamide (FITM, a negative allosteric modulator) and its twelve close structural analogs with a broad spectrum of affinities (2.4 nM < IC50 > 10 000 nM) were investigated using quantum mechanical methods. The our own N‐layered integrated molecular orbital and molecular mechanics (ONIOM) was used to optimize the molecular geometries of the receptor with complexed ligands, which were then used to perform the ab initio calculations using the fragment molecular orbitals method with energy decomposition analysis (FMO‐EDA). The results clearly showed that residues Q6603.28 and/or Y8056.55 were the anchoring points for all the studied analogs of FITM, while the H‐bond with T8157.38 determined only the orientation of very active molecules containing an amino substituent in the pyrimidine moiety (e.g., FITM). The orientation of the other parts of ligands resulted from hydrophobic interactions mainly with L7575.44, F8016.51, or W7986.48. The applied ONIOM/FMO–EDA approach facilitated the study of effects related to very small changes in the ligand structure and led to conclusions regarding the significance of individual interactions in the allosteric binding pocket of mGluR1.

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“…The key amino acids Asp10 in L-DEX YL (Asp17 in dehalogenase type II KLPN_25) have shown to play a role as a nucleophile α-carbon of the substrate to form an ester intermediate in the L-haloacid dehalogenase mechanism (Kondo et al, 2015). The role of Thr14 in L-DEX YL (Thr21 in dehalogenase type II), is not yet determined, however it was reported to firmly hold the Asp10 in a position that favours the nucleophilic attack (Ridder et al, 1997).…”

Section: Pairwise Analysismentioning

confidence: 99%

Isolation of Klebsiella pneumoniae from Sungai Skudai and in silico analysis of putative dehalogenase protein

.¹,

Wahab²,

Shariff³

et al. 2021

MJM

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Aims:The surplus use of herbicide Dalapon ® contains 2,2-dichloropropionic acid (2,2-DCP) poses great danger to human and ecosystem due to its toxicity. Hence, this study focused on the isolation and characterization of a dehalogenase producing bacteria from Sungai Skudai, Johor, capable of utilizing 2,2-DCP as a carbon source and in silico analysis of its putative dehalogenase. Methodology and results: Isolation of the target bacteria was done by using 2,2-DCP-enriched culture as the sole carbon source that allows a bacterium to grow in 20 mM of 2,2-DCP at 30 °C with the corresponding doubling time of 8.89 ± 0.03 h. The isolated bacterium was then designated as Klebsiella pneumoniae strain YZ based on biochemical tests and basic morphological examination. The full genome of K. pneumoniae strain KLPN_25 (accession number: RRE04903) which obtained from NCBI database was screened for the presence of dehalogenase gene, assuming both strains YZ and KLPN_25 were the same organisms. A putative dehalogenase gene was then identified as type II dehalogenase from the genome sequence of strain KLPN_25. The protein structure of the type II dehalogenase of KLPN_25 strain was then pairwise aligned with the crystal structure of L-2-haloacid dehalogenase (L-DEX) Pseudomonas sp. strain YL as the template, revealing the existence of conserved amino acids residues, uniquely known to participate in the dehalogenation mechanism. The finding thus implies that the amino acid residues of type II dehalogenase possibly shares similar catalytic functions with the L-DEX. Conclusion, significance and impact of the study: In conclusion, this study confirmed the presence of new dehalogenase from the genus Klebsiella with potential to degrade 2,2-DCP from the river water. The structural information of type II dehalogenase provides insights for future work in designing haloacid dehalogenases.

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Theoretical prediction and experimental verification on enantioselectivity of haloacid dehalogenase l-DEX YL with chloropropionate

Cited by 9 publications

References 33 publications

Mini Review: Advances in 2-Haloacid Dehalogenases

Mini Review: Advances in 2-Haloacid Dehalogenases

ONIOM and FMO‐EDA study of metabotropic glutamate receptor 1: Quantum insights into the allosteric binding site

Isolation of Klebsiella pneumoniae from Sungai Skudai and in silico analysis of putative dehalogenase protein

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