Functionally relevant motions of haloalkane dehalogenases occur in the specificity-modulating cap domains
| Authors | |
|---|---|
| Year of publication | 2002 |
| Type | Article in Periodical |
| Magazine / Source | Protein Science |
| MU Faculty or unit | |
| Citation | |
| Web | http://ncbr.chemi.muni.cz/~jiri/ABSTRACTS/protsci02.html |
| Field | Biochemistry |
| Keywords | MOLECULAR DYNAMICS; SIMULATION; MOTION; DEHALOGENASE; CATALYSIS |
| Description | One nanosecond molecular dynamics trajectories of three haloalkane dehalogenases (DhlA, LinB and DhaA) are compared. The main domain was rigid in all three dehalogenases, while the substrate specificity-modulating cap domains showed considerably higher mobility. The functionally relevant motions were spread over entire cap domain in DhlA, while were more localized in LinB and DhaA. The highest amplitude of essential motions of DhlA was noted in the alpha4-helix-loop-alpha4-helix region, formerly proposed to participate in the large conformation change needed for product release. The highest amplitude of essential motions of LinB and DhaA was observed in the random coil prior to helix 4 linking two domains of these proteins. This flexibility is the consequence of modular composition of haloalkane dehalogenases. Two members of the catalytic triad, i.e. the nucleophile and the base, showed very high level of rigidity in all three dehalogenases. This rigidity is essential for their function. One of the halide-stabilizing residues, important for the catalysis, shows significantly higher flexibility in DhlA compared to LinB and DhaA. Enhanced flexibility may be required for destabilization of the electrostatic interactions during the release of the halide ion from the deeply buried active site of DhlA. Exchange of water molecules between the enzyme active site and bulk solvent was very different among three dehalogenases. The differences could be related the flexibility of the cap domains and to the number of entrance tunnels. |
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