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ID: 16625.0, MPI für biophysikalische Chemie / Theoretische und computergestützte Biophysik (Dr. Helmut Grubmüller)
Mechanism of hyaluronan degradation by Streptococcus pneumoniae hyaluronate lyase - Structures of complexes with the substrate
Authors:Jedrzejas, M. J.; Mello, L. V.; de Groot, B. L.; Li, S. L.
Date of Publication (YYYY-MM-DD):2002-08-02
Title of Journal:Journal of Biological Chemistry
Issue / Number:31
Start Page:28287
End Page:28297
Review Status:Peer-review
Audience:Not Specified
Abstract / Description: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.
Comment of the Author/Creator:Date: 2002, AUG 2
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für biophysikalische Chemie/AG Bert de Groot
External Affiliations:Childrens Hosp Oakland, Res Inst, 5700 Martin Luther King Jr; Way, Oakland, CA 94609 USA; Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA; Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA; Natl Ctr Genet Resources & Biotechnol, BR-70770900 Brasilia, DF, Brazil
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