Mechanism of Enhanced Conversion of 1,2,3-Trichloropropane by Mutant Haloalkane Dehalogenase Revealed by Molecular Modeling.

BANÁŠ, Pavel, Michal OTYEPKA, Jitka VÉVODOVÁ, Petr JEŘÁBEK, Michal BOHÁČ, Martin PETŘEK and Jiří DAMBORSKÝ. Mechanism of Enhanced Conversion of 1,2,3-Trichloropropane by Mutant Haloalkane Dehalogenase Revealed by Molecular Modeling. JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN. 2006, vol. 20, No 9, p. 375-383. ISSN 0920-654X.

Basic information

• Original name: Mechanism of Enhanced Conversion of 1,2,3-Trichloropropane by Mutant Haloalkane Dehalogenase Revealed by Molecular Modeling.
• Name in Czech: Molekulární mechanismus urzchlené konverze 1,2,3-trichloropropanu prostřednictvím mutantu haloalkandehalogenázy odhaleného strukturní a počítačovou analýzou.
• Authors: BANÁŠ, Pavel (203 Czech Republic), Michal OTYEPKA (203 Czech Republic), Jitka VÉVODOVÁ (203 Czech Republic), Petr JEŘÁBEK (203 Czech Republic), Michal BOHÁČ (203 Czech Republic), Martin PETŘEK (203 Czech Republic) and Jiří DAMBORSKÝ (203 Czech Republic, guarantor).
• Edition: JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 2006, 0920-654X.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10600 1.6 Biological sciences
• Country of publisher: Switzerland
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 2.089
• RIV identification code: RIV/00216224:14310/06:00017448
• Organization unit: Faculty of Science
• UT WoS: 000241900000003
• Keywords in English: 1.2.3-Trichloropropane (TCP); halogenated compounds; DhaA; Rhodococcus sp
• Tags: 1.2.3-Trichloropropane (TCP), DhaA, Halogenated Compounds, Rhodococcus sp
• Tags: Reviewed

Abstract

1,2,3-Trichloropropane (TCP) is a highly toxic, recalcitrant byproduct of epichlorohydrin manufacture. Haloalkane dehalogenase (DhaA) from Rhodococcus sp. hydrolyses the carbon-halogen bond in various halogenated compounds including TCP, but with low efficiency (kcat/Km = 36 s-1M-1). A Cys176Tyr-DhaA mutant with a three-fold higher catalytic efficiency for TCP dehalogenation has been previously obtained by error-prone PCR. We have used molecular simulations and quantum mechanical calculations to elucidate the molecular mechanisms involved in the improved catalysis of the mutant, and enantioselectivity of DhaA towards TCP. The Cys176Tyr mutation modifies the protein access and export routes. Substitution of the Cys residue by the bulkier Tyr narrows the upper tunnel, making the second tunnel "slot" the preferred route. TCP can adopt two major orientations in the DhaA enzyme, in one of which the halide-stabilizing residue Asn41 forms a hydrogen bond with the terminal halogen atom of the TCP molecule, while in the other it bonds with the central halogen atom. The differences in these binding patterns explain the preferential formation of the (R)- over the (S)-enantiomer of 2,3-dichloropropane-1-ol in the reaction catalyzed by the enzyme.

Abstract (in Czech)

1,2,3-Trichloropropane (TCP) je vysoce toxický vedlejší produkt pri výrobě epichlorohydrinu. Haloalkán dehalogenáza (DhaA) bakterie Rhodococcus sp.hydrolyzuje vazbu uhlík-halogen na různé halogenované sloučeniny, zahrnující i TCP.

Links

• MSM0021622412, plan (intention): Name: Interakce mezi chemickými látkami, prostředím a biologickými systémy a jejich důsledky na globální, regionální a lokální úrovni (INCHEMBIOL) (Acronym: INCHEMBIOL)

Investor: Ministry of Education, Youth and Sports of the CR, Interactions among the chemicals, environment and biological systems and their consequences on the global, regional and local scales (INCHEMBIOL)