Protein-ligand interactions in haloalkane dehalogenases

Michal Kutý1,2, David Řeha1,2, and Ivana Kuta Smatanova1,2

1Faculty of Science, University of South Bohemia in Ceske Budejovice, Branisovska 31, 370 05 Ceske Budejovice, Czech Republic
2Center for Nanobiology and Structural Biology, Institute of Microbiology of the Academy of Sciences, Czech Republic, 142 20 Prague, Czech Republic

kutym@seznam.cz

 

Haloalkane dehalogenases (HLDs) are  enzymes  that catalyze reactions of great environmental and biotechnological significance. HLDs  (EC  3.8.1.5)  belong to the a/b-hydrolase superfamily [1] of enzymes  catalyzing hydrolytic  cleavage  of  carbon-halogen  bonds  in halogenated  hydrocarbons  to  yield  the  corresponding  alcohol,  a proton and a halide [2]. This work is focused on the protein-ligand interactions in a recently  constructed  stable  and  solvent-resistant  haloalkane  dehalogenase  DhaA from  Rhodococcus  rhodochrous  NCIMB  13064 and its variants with mutations in the residues that form the access tunnel connecting the enzyme’s buried active  site  to  the  surrounding  solvent. The interactions and different binding sites between a protein and a ligand were studied by using molecular dynamics method GROMACS [3] and PELE [4,5] (an acronym Protein Energy Landscape Exploration) that combines a Monte Carlo stochastic approach with protein structure prediction and is capable of accurately reproducing long time scale processes.  

 

This research is supported by the GACR (P207/12/0775).

 

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3.   Van Der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJ (2005). "GROMACS: fast, flexible, and free". J Comput Chem 26 (16): 1701–18.

4.   PELE: Protein energy landscape exploration. A novel Monte Carlo based technique (2005), J. Chem. Theo. Comput., 1(6):1304-1311.

5.   PELE web server: atomistic study of biomolecular systems at your fingertips (2013), Nucleic Acids Research, 41(W1):W322-W328.