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Rup Lal - One of the best experts on this subject based on the ideXlab platform.
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compound specific isotope analysis and enantiomer fractionation to characterize the transformation of Hexachlorocyclohexane isomers in a soil wheat pot system
Environmental Science & Technology, 2020Co-Authors: Xiao Liu, Rup Lal, Steffen Kummel, Ines Merbach, Hans H RichnowAbstract:The uptake by plant from soil is one of the first steps for Hexachlorocyclohexane isomers (HCHs) to enter the food web. However, the HCH transformation associated with the uptake process is still n...
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Kinetic and Sequence-Structure-Function Analysis of LinB Enzyme Variants with β- and δ-Hexachlorocyclohexane
PLoS ONE, 2014Co-Authors: Rinku Pandey, Rup Lal, Del Lucent, Kirti Kumari, Pooja Sharma, John G. Oakeshott, Gunjan PandeyAbstract:Organochlorine insecticide Hexachlorocyclohexane (HCH) has recently been classified as a 'Persistent Organic pollutant' by the Stockholm Convention. The LinB haloalkane dehalogenase is a key upstream enzyme in the recently evolved Lin pathway for the catabolism of HCH in bacteria. Here we report a sequence-structure-function analysis of ten naturally occurring and thirteen synthetic mutants of LinB. One of the synthetic mutants was found to have ∼80 fold more activity for β- and δ-Hexachlorocyclohexane. Based on detailed biophysical calculations, molecular dynamics and ensemble docking calculations, we propose that the latter variant is more active because of alterations to the shape of its active site and increased conformational plasticity.
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Hexachlorocyclohexane: persistence, toxicity and decontamination.
Reviews on Environmental Health, 2014Co-Authors: Namita Nayyar, Helianthous Verma, Roshan Kumar, Nitish Kumar Mahato, Naseer Sangwan, Puneet Kohli, Vivek Negi, Phoebe Oldach, Vipin Gupta, Rup LalAbstract:Hexachlorocyclohexane (HCH), a persistent organochlorine insecticide, has been extensively used in the past for control of agricultural pests and vector borne diseases. The use of HCH has indeed accrued benefits, however the unusual production of the insecticidal isomer; γ-HCH (lindane) and unregulated disposal of HCH muck has created various dumpsites all over the world, leading to serious environmental concerns. HCH isomers have been ranked as possible human carcinogens and endocrine disruptors with proven teratogenic, mutagenic and genotoxic effects, hence making its decontamination mandatory. Efforts in this direction have led to the isolation of various HCH degrading bacteria from the dumpsites, reflecting their role in HCH bioremediation. This review summarizes the problem of environmental persistence of HCH isomers along with their toxicity and possible solutions for their decontamination.
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Draft Genome Sequence of a Hexachlorocyclohexane-Degrading Bacterium, Sphingobium baderi Strain LL03T.
Genome Announcements, 2013Co-Authors: Jasvinder Kaur, Helianthous Verma, Charu Tripathi, Jitendra P. Khurana, Rup LalAbstract:ABSTRACT Sphingobium baderi strain LL03T was isolated from Hexachlorocyclohexane (HCH)-contaminated soil from Spolana, Czech Republic. Strain LL03T is a mutant that is deficient in linB and linC (genes that encode Hexachlorocyclohexane haloalkane dehalogenase and dehydrogenase, respectively). The draft genome sequence of LL03T (~4.85 Mb) consists of 92 contigs and 4,914 coding sequences, with a G+C content of 63.5%.
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Draft Genome Sequence of Sphingobium sp. Strain HDIPO4, an Avid Degrader of Hexachlorocyclohexane.
Genome Announcements, 2013Co-Authors: Udita Mukherjee, Jitendra P. Khurana, Roshan Kumar, Nitish Kumar Mahato, Rup LalAbstract:Sphingobium sp. strain HDIPO4 was isolated from a Hexachlorocyclohexane (HCH) dumpsite and degraded HCH isomers rapidly. The draft genome sequence of HDIPO4 (~4.7 Mbp) contains 143 contigs and 4,646 coding sequences with a G+C content of 65%.
Cristina Suñol - One of the best experts on this subject based on the ideXlab platform.
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Allosteric interactions between γ-aminobutyric acid, benzodiazepine and picrotoxinin binding sites in primary cultures of cerebellar granule cells. Differential effects induced by γ- and δ-Hexachlorocyclohexane
European Journal of Pharmacology, 1997Co-Authors: Carmen Vale, Anna Pomés, Eduard Rodríguez-farré, Cristina SuñolAbstract:Allosterism between γ-aminobutyric acid (GABA), benzodiazepine and picrotoxinin recognition sites on the GABAA receptor was studied in primary cultures of cerebellar granule cells. The increase in [3H]flunitrazepam binding induced by GABA was inhibited by bicuculline and picrotoxinin and the decrease in [35S]t-butylbicyclophosphorothionate ([35S]TBPS) binding mediated by GABA was reverted by bicuculline. The effects of Hexachlorocyclohexanes (the convulsant γ- and the depressant δ-isomers, both acting at the picrotoxinin recognition site) on GABA and benzodiazepine sites were studied. δ-Hexachlorocyclohexane, but not the γ-isomer (lindane), increased [3H]flunitrazepam binding in a concentration-dependent manner (EC50: 8.3 μM). This increase in [3H]flunitrazepam binding was reduced by bicuculline and picrotoxinin. The γ-isomer reduced the increase in [3H]flunitrazepam binding induced by GABA or δ-Hexachlorocyclohexane. Neither δ- nor γ-Hexachlorocyclohexane inhibited [3H]GABA binding. Moreover, the inhibition of [35S]TBPS binding induced by δ-Hexachlorocyclohexane was not reverted by bicuculline. The results obtained in this study in vitro agree with the pharmacological properties and the effects of γ- and δ-Hexachlorocyclohexane in vivo. It is concluded that δ-Hexachlorocyclohexane acts as a positive allosteric modulator and γ-Hexachlorocyclohexane acts as a non-competitive antagonist of the GABAA receptor.
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Allosteric interactions between gamma-aminobutyric acid, benzodiazepine and picrotoxinin binding sites in primary cultures of cerebellar granule cells. Differential effects induced by gamma- and delta-Hexachlorocyclohexane.
European Journal of Pharmacology, 1997Co-Authors: Carmen Vale, Anna Pomés, Eduard Rodríguez-farré, Cristina SuñolAbstract:Allosterism between gamma-aminobutyric acid (GABA), benzodiazepine and picrotoxinin recognition sites on the GABAA receptor was studied in primary cultures of cerebellar granule cells. The increase in [3H]flunitrazepam binding induced by GABA was inhibited by bicuculline and picrotoxinin and the decrease in [35S]t-butylbicyclophosphorothionate ([35S]TBPS) binding mediated by GABA was reverted by bicuculline. The effects of Hexachlorocyclohexanes (the convulsant gamma- and the depressant delta-isomers, both acting at the picrotoxinin recognition site) on GABA and benzodiazepine sites were studied. delta-Hexachlorocyclohexane, but not the gamma-isomer (lindane), increased [3H]flunitrazepam binding in a concentration-dependent manner (EC50: 8.3 microM). This increase in [3H]flunitrazepam binding was reduced by bicuculline and picrotoxinin. The gamma-isomer reduced the increase in [3H]flunitrazepam binding induced by GABA or delta-Hexachlorocyclohexane. Neither delta- nor gamma-Hexachlorocyclohexane inhibited [3H]GABA binding. Moreover, the inhibition of [35S]TBPS binding induced by delta-Hexachlorocyclohexane was not reverted by bicuculline. The results obtained in this study in vitro agree with the pharmacological properties and the effects of gamma- and delta-Hexachlorocyclohexane in vivo. It is concluded that delta-Hexachlorocyclohexane acts as a positive allosteric modulator and gamma-Hexachlorocyclohexane acts as a non-competitive antagonist of the GABAA receptor.
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Stimulation of Phosphoinositide Hydrolysis by γ- and δ-Hexachlorocyclohexane in Primary Cultures of Cerebellar Granule Cells: Interaction with Glutamate and Carbachol Receptor-Mediated Phosphoinositide Response and Effects of Specific Pharmacological
Pesticide Biochemistry and Physiology, 1996Co-Authors: Coral Sanfeliu, Eduard Rodríguez-farré, Cristina Suñol, R Rosa, Rosa CristòfolAbstract:Abstract The accumulation of [ 3 H]inositol phosphates derived from phosphoinositide hydrolysis stimulated by γ- and δ-Hexachlorocyclohexane isomers was characterized in primary cultures of cerebellar granule cells. The EC 50 for γ- and δ-Hexachlorocyclohexane was 106 and 85 μ M, respectively. Stimulatory effects of Hexachlorocyclohexane isomers were highly dependent on extracellular Ca 2+ but they were not inhibited by classical voltage-sensitive Ca 2+ and Na + channel blockers. The Na + /Ca 2+ exchanger blocker amiloride caused a significant inhibition of δ-Hexachlorocyclohexane effects. A lack of additive effects on phosphoinositide hydrolysis stimulation between Hexachlorocyclohexane isomers and depolarization by high K + was observed. The effects of each Hexachlorocyclohexane isomer on glutamate or carbachol-induced inositol phosphate stimulation were also not additive, whereas that of high K + was less than additive or synergistic when combined with glutamate or carbachol, respectively. When neuronal cells were exposed to the combination of δ-Hexachlorocyclohexane and glutamate or carbachol in the presence of the respective receptor antagonists only the δ-Hexachlorocyclohexane stimulatory effect was observed. Thus, the inhibition of glutamate- and carbachol-stimulated phosphoinositide hydrolysis by δ-Hexachlorocyclohexane seems to imply a receptor-independent mechanism. It is suggested that both γ- and δ-Hexachlorocyclohexane activate phosphoinositide-specific phospholipase C partly through Ca 2+ -related mechanisms.
Eduard Rodríguez-farré - One of the best experts on this subject based on the ideXlab platform.
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Allosteric interactions between γ-aminobutyric acid, benzodiazepine and picrotoxinin binding sites in primary cultures of cerebellar granule cells. Differential effects induced by γ- and δ-Hexachlorocyclohexane
European Journal of Pharmacology, 1997Co-Authors: Carmen Vale, Anna Pomés, Eduard Rodríguez-farré, Cristina SuñolAbstract:Allosterism between γ-aminobutyric acid (GABA), benzodiazepine and picrotoxinin recognition sites on the GABAA receptor was studied in primary cultures of cerebellar granule cells. The increase in [3H]flunitrazepam binding induced by GABA was inhibited by bicuculline and picrotoxinin and the decrease in [35S]t-butylbicyclophosphorothionate ([35S]TBPS) binding mediated by GABA was reverted by bicuculline. The effects of Hexachlorocyclohexanes (the convulsant γ- and the depressant δ-isomers, both acting at the picrotoxinin recognition site) on GABA and benzodiazepine sites were studied. δ-Hexachlorocyclohexane, but not the γ-isomer (lindane), increased [3H]flunitrazepam binding in a concentration-dependent manner (EC50: 8.3 μM). This increase in [3H]flunitrazepam binding was reduced by bicuculline and picrotoxinin. The γ-isomer reduced the increase in [3H]flunitrazepam binding induced by GABA or δ-Hexachlorocyclohexane. Neither δ- nor γ-Hexachlorocyclohexane inhibited [3H]GABA binding. Moreover, the inhibition of [35S]TBPS binding induced by δ-Hexachlorocyclohexane was not reverted by bicuculline. The results obtained in this study in vitro agree with the pharmacological properties and the effects of γ- and δ-Hexachlorocyclohexane in vivo. It is concluded that δ-Hexachlorocyclohexane acts as a positive allosteric modulator and γ-Hexachlorocyclohexane acts as a non-competitive antagonist of the GABAA receptor.
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Allosteric interactions between gamma-aminobutyric acid, benzodiazepine and picrotoxinin binding sites in primary cultures of cerebellar granule cells. Differential effects induced by gamma- and delta-Hexachlorocyclohexane.
European Journal of Pharmacology, 1997Co-Authors: Carmen Vale, Anna Pomés, Eduard Rodríguez-farré, Cristina SuñolAbstract:Allosterism between gamma-aminobutyric acid (GABA), benzodiazepine and picrotoxinin recognition sites on the GABAA receptor was studied in primary cultures of cerebellar granule cells. The increase in [3H]flunitrazepam binding induced by GABA was inhibited by bicuculline and picrotoxinin and the decrease in [35S]t-butylbicyclophosphorothionate ([35S]TBPS) binding mediated by GABA was reverted by bicuculline. The effects of Hexachlorocyclohexanes (the convulsant gamma- and the depressant delta-isomers, both acting at the picrotoxinin recognition site) on GABA and benzodiazepine sites were studied. delta-Hexachlorocyclohexane, but not the gamma-isomer (lindane), increased [3H]flunitrazepam binding in a concentration-dependent manner (EC50: 8.3 microM). This increase in [3H]flunitrazepam binding was reduced by bicuculline and picrotoxinin. The gamma-isomer reduced the increase in [3H]flunitrazepam binding induced by GABA or delta-Hexachlorocyclohexane. Neither delta- nor gamma-Hexachlorocyclohexane inhibited [3H]GABA binding. Moreover, the inhibition of [35S]TBPS binding induced by delta-Hexachlorocyclohexane was not reverted by bicuculline. The results obtained in this study in vitro agree with the pharmacological properties and the effects of gamma- and delta-Hexachlorocyclohexane in vivo. It is concluded that delta-Hexachlorocyclohexane acts as a positive allosteric modulator and gamma-Hexachlorocyclohexane acts as a non-competitive antagonist of the GABAA receptor.
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Stimulation of Phosphoinositide Hydrolysis by γ- and δ-Hexachlorocyclohexane in Primary Cultures of Cerebellar Granule Cells: Interaction with Glutamate and Carbachol Receptor-Mediated Phosphoinositide Response and Effects of Specific Pharmacological
Pesticide Biochemistry and Physiology, 1996Co-Authors: Coral Sanfeliu, Eduard Rodríguez-farré, Cristina Suñol, R Rosa, Rosa CristòfolAbstract:Abstract The accumulation of [ 3 H]inositol phosphates derived from phosphoinositide hydrolysis stimulated by γ- and δ-Hexachlorocyclohexane isomers was characterized in primary cultures of cerebellar granule cells. The EC 50 for γ- and δ-Hexachlorocyclohexane was 106 and 85 μ M, respectively. Stimulatory effects of Hexachlorocyclohexane isomers were highly dependent on extracellular Ca 2+ but they were not inhibited by classical voltage-sensitive Ca 2+ and Na + channel blockers. The Na + /Ca 2+ exchanger blocker amiloride caused a significant inhibition of δ-Hexachlorocyclohexane effects. A lack of additive effects on phosphoinositide hydrolysis stimulation between Hexachlorocyclohexane isomers and depolarization by high K + was observed. The effects of each Hexachlorocyclohexane isomer on glutamate or carbachol-induced inositol phosphate stimulation were also not additive, whereas that of high K + was less than additive or synergistic when combined with glutamate or carbachol, respectively. When neuronal cells were exposed to the combination of δ-Hexachlorocyclohexane and glutamate or carbachol in the presence of the respective receptor antagonists only the δ-Hexachlorocyclohexane stimulatory effect was observed. Thus, the inhibition of glutamate- and carbachol-stimulated phosphoinositide hydrolysis by δ-Hexachlorocyclohexane seems to imply a receptor-independent mechanism. It is suggested that both γ- and δ-Hexachlorocyclohexane activate phosphoinositide-specific phospholipase C partly through Ca 2+ -related mechanisms.
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Hippocampal noradrenaline release is modulated by γ- and δ-Hexachlorocyclohexane isomers: which mechanisms are involved?
European Journal of Pharmacology, 1994Co-Authors: Rosa Cristòfol, Eduard Rodríguez-farréAbstract:Abstract The differential effects of γ- and δ-Hexachlorocyclohexane isomers on 25 mM K + -evoked release of [ 3 H]noradrenaline were studied in hippocampal slices treated with selected agents to activate or block L- and N-type Ca 2+ and Na + voltage-sensitive ion channels, Cl − transport and Ca 2+ -dependent protein activity. At maximally effective concentrations, the L- and N-type Ca 2+ channel blockers nifedipine and ω-conotoxin, respectively, and the Na + channel antagonist tetrodotoxin did not modify the enhancement of K + -evoked [ 3 H]noradrenaline release induced by γ-Hexachlorocyclohexane. Likewise, under activation of protein kinase C by phorbol 12,13-dibutyrate (PDB) or inhibition of calmodulin by N -(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), the stimulatory effect of γ-Hexachlorocyclohexane remained almost unchanged. The Cl − transport blocker 4,4-diisothiocyanato-stilbene-2,2′-disulfonic acid (DIDS) significantly reduced the effect of γ-Hexachlorocyclohexane on [ 3 H]noradrenaline release. The enhanced release in the presence of Bay K 8644, the L-type Ca 2+ channel activator, was significantly inhibited by nifedipine but not by δ-Hexachlorocyclohexane. The combination of ω-conotoxin and tetrodotoxin with δ-Hexachlorocyclohexane did not alter the [ 3 H]noradrenaline release effects of each agent alone. Activation of protein kinase C in the presence of δ-Hexachlorocyclohexane resulted in a reduction of the δ isomer effect and in a potentiation of the PDB effect. W-7 did not further facilitate the inhibition induced by δ-Hexachlorocyclohexane alone. These data suggest that Hexachlorocyclohexane isomers may modify K + -evoked [ 3 H]noradrenaline release by interacting with presynaptic molecular processes involving changes in Cl − membrane permeability and intracellular Ca 2+ homeostasis.
Hans-peter E. Kohler - One of the best experts on this subject based on the ideXlab platform.
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Important amino acid residues of Hexachlorocyclohexane dehydrochlorinases (LinA) for enantioselective transformation of Hexachlorocyclohexane isomers
Biodegradation, 2017Co-Authors: Nidhi Shrivastava, Ankit S. Macwan, Hans-peter E. Kohler, Ashwani KumarAbstract:LinA-type1 and LinA-type2 are two well-characterized variants of the enzyme ‘Hexachlorocyclohexane (HCH)-dehydrochlorinase’. They differ from each other at ten amino acid positions and exhibit differing enantioselectivity for the transformation of the (–) and (+) enantiomers of α-HCH. Amino acids responsible for this enantioselectivity, however, are not known. An in silico docking analysis identified four amino acids (K20, L96, A131, and T133) in LinA-type1 that could be involved in selective binding of the substrates. Experimental studies with constructed mutant enzymes revealed that a combined presence of three amino acid changes in LinA-type1, i.e. K20Q, L96C, and A131G, caused a reversal in its preference from the (–) to the (+) enantiomer of α-HCH. This preference was enhanced by the additional amino acid change T133 M. Presence of these four changes also caused the reversal of enantioselectivity of LinA-type1 for δ-HCH, and β-, γ-, and δ-pentachlorocyclohexens. Thus, the residues K20, L96, A131, and T133 in LinA-type1 and the residues Q20, C96, G131, and M133 in LinA-type 2 appear to be important determinants for the enantioselectivity of LinA enzymes.
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Enzymatic conversion of ε-Hexachlorocyclohexane and a heptachlorocyclohexane isomer, two neglected components of technical Hexachlorocyclohexane.
Environmental Science & Technology, 2012Co-Authors: Kiran Bala, Thomas Poiger, Birgit Geueke, Milena E. Miska, Daniel Rentsch, Mandeep Dadhwal, Christoph Holliger, Hans-peter E. KohlerAbstract:α-, β, γ-, and δ-Hexachlorocyclohexane (HCH), the four major isomers of technical HCH, are susceptible to biotic transformations, whereby only α- and γ-HCH undergo complete mineralization. Nevertheless, LinA and LinB catalyzing HCl elimination and hydrolytic dehalogenations, respectively, as initial steps in the mineralization also convert β- and δ-HCH to a variety of mainly hydroxylated metabolites. In this study, we describe the isolation of two minor components of technical HCH, e-HCH, and heptachlorocyclohexane (HeCH), and we present data on enzymatic transformations of both compounds by two dehydrochlorinases (LinA1 and LinA2) and a haloalkane dehalogenase (LinB) from Sphingobium indicum B90A. In contrast to reactions with α-, γ-, and δ-HCH, both LinA enzymes converted e-HCH to a mixture of 1,2,4-, 1,2,3-, and 1,3,5-trichlorobenzenes without the accumulation of pentachlorocyclohexene as intermediate. Furthermore, both LinA enzymes were able to convert HeCH to a mixture of 1,2,3,4- and 1,2,3,5-tetrach...
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enzymatic conversion of e Hexachlorocyclohexane and a heptachlorocyclohexane isomer two neglected components of technical Hexachlorocyclohexane
Environmental Science & Technology, 2012Co-Authors: Kiran Bala, Thomas Poiger, Rup Lal, Birgit Geueke, Milena E. Miska, Daniel Rentsch, Mandeep Dadhwal, Christoph Holliger, Hans-peter E. KohlerAbstract:α-, β, γ-, and δ-Hexachlorocyclohexane (HCH), the four major isomers of technical HCH, are susceptible to biotic transformations, whereby only α- and γ-HCH undergo complete mineralization. Nevertheless, LinA and LinB catalyzing HCl elimination and hydrolytic dehalogenations, respectively, as initial steps in the mineralization also convert β- and δ-HCH to a variety of mainly hydroxylated metabolites. In this study, we describe the isolation of two minor components of technical HCH, e-HCH, and heptachlorocyclohexane (HeCH), and we present data on enzymatic transformations of both compounds by two dehydrochlorinases (LinA1 and LinA2) and a haloalkane dehalogenase (LinB) from Sphingobium indicum B90A. In contrast to reactions with α-, γ-, and δ-HCH, both LinA enzymes converted e-HCH to a mixture of 1,2,4-, 1,2,3-, and 1,3,5-trichlorobenzenes without the accumulation of pentachlorocyclohexene as intermediate. Furthermore, both LinA enzymes were able to convert HeCH to a mixture of 1,2,3,4- and 1,2,3,5-tetrach...
Mrutyunjay Suar - One of the best experts on this subject based on the ideXlab platform.
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enantioselective transformation of α Hexachlorocyclohexane by the dehydrochlorinases lina1 and lina2 from the soil bacterium sphingomonas paucimobilis b90a
Applied and Environmental Microbiology, 2005Co-Authors: Mrutyunjay Suar, Andrea Hauser, Thomas Poiger, Hansrudolf Buser, Markus D Muller, Charu Dogra, Vishakha Raina, Christof Holliger, Jan Roelof Van Der MeerAbstract:Sphingomonas paucimobilis B90A contains two variants, LinA1 and LinA2, of a dehydrochlorinase that catalyzes the first and second steps in the metabolism of Hexachlorocyclohexanes (R. Kumari, S. Subudhi, M. Suar, G. Dhingra, V. Raina, C. Dogra, S. Lal, J. R. van der Meer, C. Holliger, and R. Lal, Appl. Environ. Microbiol. 68:6021-6028, 2002). On the amino acid level, LinA1 and LinA2 were 88% identical to each other, and LinA2 was 100% identical to LinA of S. paucimobilis UT26. Incubation of chiral α-Hexachlorocyclohexane (α-HCH) with Escherichia coli BL21 expressing functional LinA1 and LinA2 S-glutathione transferase fusion proteins showed that LinA1 preferentially converted the (+) enantiomer, whereas LinA2 preferred the (−) enantiomer. Concurrent formation and subsequent dissipation of β-pentachlorocyclohexene enantiomers was also observed in these experiments, indicating that there was enantioselective formation and/or dissipation of these enantiomers. LinA1 preferentially formed (3S,4S,5R,6R)-1,3,4,5,6-pentachlorocyclohexene, and LinA2 preferentially formed (3R,4R,5S,6S)-1,3,4,5,6-pentachlorocyclohexene. Because enantioselectivity was not observed in incubations with whole cells of S. paucimobilis B90A, we concluded that LinA1 and LinA2 are equally active in this organism. The enantioselective transformation of chiral α-HCH by LinA1 and LinA2 provides the first evidence of the molecular basis for the changed enantiomer composition of α-HCH in many natural environments. Enantioselective degradation may be one of the key processes determining enantiomer composition, especially when strains that contain only one of the linA genes, such as S. paucimobilis UT26, prevail.