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

J 2006

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 et al.

Základní údaje

Originální název

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

Název česky

Molekulární mechanismus urzchlené konverze 1,2,3-trichloropropanu prostřednictvím mutantu haloalkandehalogenázy odhaleného strukturní a počítačovou analýzou.

Autoři

BANÁŠ, Pavel; Michal OTYEPKA; Jitka VÉVODOVÁ; Petr JEŘÁBEK; Michal BOHÁČ; Martin PETŘEK a Jiří DAMBORSKÝ

Vydání

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 2006, 0920-654X

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10600 1.6 Biological sciences

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 2.089

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/06:00017448

Organizační jednotka

Přírodovědecká fakulta

UT WoS

000241900000003

Klíčová slova anglicky

1.2.3-Trichloropropane (TCP); halogenated compounds; DhaA; Rhodococcus sp

Štítky

1.2.3-Trichloropropane (TCP), DhaA, Halogenated Compounds, Rhodococcus sp

Příznaky

Recenzováno

Změněno: 19. 3. 2010 12:17, prof. Mgr. Jiří Damborský, Dr.

Anotace

ORIG CZ

V originále

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.

Česky

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.

Návaznosti

MSM0021622412, záměr

Název: Interakce mezi chemickými látkami, prostředím a biologickými systémy a jejich důsledky na globální, regionální a lokální úrovni (INCHEMBIOL) (Akronym: INCHEMBIOL)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Interakce mezi chemickými látkami, prostředím a biologickými systémy a jejich důsledky na globální , regionální a lokální úrovni

Citovat

BANÁŠ, Pavel; Michal OTYEPKA; Jitka VÉVODOVÁ; Petr JEŘÁBEK; Michal BOHÁČ; Martin PETŘEK a 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, roč. 20, č. 9, s. 375-383. ISSN 0920-654X.

@article{700040,
   author = {Banáš, Pavel and Otyepka, Michal and Vévodová, Jitka and Jeřábek, Petr and Boháč, Michal and Petřek, Martin and Damborský, Jiří},
   article_number = {9},
   keywords = {1.2.3-Trichloropropane (TCP); halogenated compounds; DhaA; Rhodococcus sp},
   language = {eng},
   issn = {0920-654X},
   journal = {JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN},
   title = {Mechanism of Enhanced Conversion of 1,2,3-Trichloropropane by Mutant Haloalkane Dehalogenase Revealed by Molecular Modeling.},
   url = {http://loschmidt.chemi.muni.cz/peg/abstracts/jcamd06.html},
   volume = {20},
   year = {2006}
}

TY  - JOUR
ID  - 700040
AU  - Banáš, Pavel - Otyepka, Michal - Vévodová, Jitka - Jeřábek, Petr - Boháč, Michal - Petřek, Martin - Damborský, Jiří
PY  - 2006
TI  - Mechanism of Enhanced Conversion of 1,2,3-Trichloropropane by Mutant Haloalkane Dehalogenase Revealed by Molecular Modeling.
JF  - JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
VL  - 20
IS  - 9
SP  - 375-383
EP  - 375-383
SN  - 0920654X
KW  - 1.2.3-Trichloropropane (TCP)
KW  - halogenated compounds
KW  - DhaA
KW  - Rhodococcus sp
UR  - http://loschmidt.chemi.muni.cz/peg/abstracts/jcamd06.html
N2  - 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.
ER  -

BANÁŠ, Pavel; Michal OTYEPKA; Jitka VÉVODOVÁ; Petr JEŘÁBEK; Michal BOHÁČ; Martin PETŘEK a Jiří DAMBORSKÝ. Mechanism of Enhanced Conversion of 1,2,3-Trichloropropane by Mutant Haloalkane Dehalogenase Revealed by Molecular Modeling. \textit{JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN}. 2006, roč.~20, č.~9, s.~375-383. ISSN~0920-654X.

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