Domain motions of hyaluronan lyase underlying processive hyaluronan translocation.

Harshad V Joshi, Mark J Jedrzejas, Bert L de Groot

Computational Biomolecular Dynamics Group, Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany.

Proteins 2009 Jul

filter terms:

Hyaluronan lyase (Hyal) is a surface enzyme occurring in many bacterial organisms including members of Streptococcus species. Streptococcal Hyal primarily degrades hyaluronan-substrate (HA) of the extracellular matrix. This degradation appears to facilitate the spread of this bacterium throughout host tissues. Unlike purely endolytic degradation of its other substrates, unsulfated chondroitin or some chondroitin sulfates, the degradation of HA by Hyal proceeds by processive exolytic cleavage of one disaccharide at a time following an initial endolytic cut. Molecular dynamics (MD) studies of Hyal from Streptococcus pneumoniae are presented that address the enzyme's molecular mechanism of action and the role of domain motions for processive functionality. The analysis of extensive sub-microsecond MD simulations of this enzyme action on HA-substrates of different lengths and the connection between the domain dynamics of Hyal and the translocation of the HA-substrate reveals that opening/closing and twisting domain motions of the Hyal are intimately linked to processive HA degradation. Enforced simulations confirmed this finding as the domain motions in SpnHyal were found to be induced by enforced substrate translocation. These results establish the dynamic interplay between Hyal flexibility and substrate translocation and provide insight into the processive mechanism of Hyal.

Citation

Harshad V Joshi, Mark J Jedrzejas, Bert L de Groot. Domain motions of hyaluronan lyase underlying processive hyaluronan translocation. Proteins. 2009 Jul;76(1):30-46