Other formats:
BibTeX
LaTeX
RIS
@article{404590, author = {Otyepka, Michal and Damborský, Jiří}, article_number = {5}, keywords = {MOLECULAR DYNAMICS; SIMULATION; MOTION; DEHALOGENASE; CATALYSIS}, language = {eng}, issn = {0961-8368}, journal = {Protein Science}, title = {Functionally relevant motions of haloalkane dehalogenases occur in the specificity-modulating cap domains}, url = {http://ncbr.chemi.muni.cz/~jiri/ABSTRACTS/protsci02.html}, volume = {11}, year = {2002} }
TY - JOUR ID - 404590 AU - Otyepka, Michal - Damborský, Jiří PY - 2002 TI - Functionally relevant motions of haloalkane dehalogenases occur in the specificity-modulating cap domains JF - Protein Science VL - 11 IS - 5 SP - 1206 EP - 1206 SN - 09618368 KW - MOLECULAR DYNAMICS KW - SIMULATION KW - MOTION KW - DEHALOGENASE KW - CATALYSIS UR - http://ncbr.chemi.muni.cz/~jiri/ABSTRACTS/protsci02.html N2 - 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. ER -
OTYEPKA, Michal and Jiří DAMBORSKÝ. Functionally relevant motions of haloalkane dehalogenases occur in the specificity-modulating cap domains. \textit{Protein Science}. 2002, vol.~11, No~5, p.~1206-1217. ISSN~0961-8368.
|