English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Mechanism of hyaluronan degradation by Streptococcus pneumoniae hyaluronate lyase - Structures of complexes with the substrate

MPS-Authors
/persons/resource/persons73410

de Groot,  B. L.
Research Group of Theoretical Molecular Biophysics, MPI for biophysical chemistry, Max Planck Society;

External Ressource
No external resources are shared
Fulltext (public)

599541.pdf
(Publisher version), 2MB

Supplementary Material (public)
There is no public supplementary material available
Citation

Jedrzejas, M. J., Mello, L. V., de Groot, B. L., & Li, S. L. (2002). Mechanism of hyaluronan degradation by Streptococcus pneumoniae hyaluronate lyase - Structures of complexes with the substrate. Journal of Biological Chemistry, 277(31), 28287-28297. Retrieved from http://www.jbc.org/content/277/31/28287.full.pdf+html.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0012-F33A-0
Abstract
Hyaluronate lyase enzymes degrade hyaluronan, the main polysaccharide component of the host connective tissues, predominantly into unsaturated disaccharide units, thereby destroying the normal connective tissue structure and exposing the tissue cells to various endo-and exogenous factors, including bacterial toxins. The crystal structures of Streptococcus pneumoniae hyaluronate lyase with tetra- and hexasaccharide hyaluronan substrates bound in the active site were determined at 1.52- and 2.0-Angstrom resolution, respectively. Hexasaccharide is the longest substrate segment that binds entirely within the active site of these enzymes. The enzyme residues responsible for substrate binding, positioning, catalysis, and product release were thereby identified and their specific roles characterized. The involvement of three residues in catalysis, Asn(349), His(399), and Tyro(408), is confirmed, and the details of proton acceptance and donation within the catalytic machinery are described. The mechanism of processivity of the enzyme is analyzed. The flexibility (allosteric) behavior of the enzyme may be understood in terms of the results of flexibility analysis of this protein, which identified two modes of motion that are also proposed to be involved in the hyaluronan degradation process. The first motion describes an opening and closing of the catalytic cleft located between the alpha- and beta-domains. The second motion demonstrates the mobility of a binding cleft, which may facilitate the binding of the negatively charged hyaluronan to the enzyme.