UNLABELLED: The new version of the TRITON program provides user-friendly graphical tools for modeling protein mutants using the external program MODELLER and for docking ligands into the mutants using the external program AutoDock. TRITON can now be used to design ligand-binding proteins, to study protein-ligand binding mechanisms or simply to dock any ligand to a protein. AVAILABILITY: Executable files of TRITON are available free of charge for academic users at http://ncbr.chemi.muni.cz/triton/

• MeSH
• algoritmy MeSH
• chemické modely * MeSH
• ligandy MeSH
• molekulární modely * MeSH
• počítačová grafika * MeSH
• počítačová simulace MeSH
• proteinové inženýrství metody   MeSH
• proteiny chemie   ultrastruktura   MeSH
• racionální návrh léčiv MeSH
• software * MeSH
• uživatelské rozhraní počítače MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ligandy MeSH
• proteiny MeSH

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 (k (cat)/K (m )= 36 s(-1) M(-1)). A Cys176Tyr-DhaA mutant with a threefold 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 toward 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.

• MeSH
• hydrolasy genetika   metabolismus   MeSH
• molekulární modely * MeSH
• mutace MeSH
• polymerázová řetězová reakce MeSH
• propan analogy a deriváty   chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1,2,3-trichloropropane MeSH Prohlížeč
• haloalkane dehalogenase MeSH Prohlížeč
• hydrolasy MeSH
• propan MeSH