title: Mechanism of hyaluronan binding and degradation: structure of Streptococcus pneumoniae hyaluronate lyase in complex with hyaluronic acid disaccharide at 1.7 A resolution.
abstract: Hyaluronic acid (HA) is an important constituent of the extracellular matrix; its bacterial degradation has been postulated to contribute to the spread of certain streptococci through tissue. Pneumococci and other streptococci produce hyaluronate lyase, an enzyme which depolymerizes HA, thus hyaluronate lyase might contribute directly to bacterial invasion. Although two different mechanisms for lyase action have been proposed, there was no crystallographic evidence to support those mechanisms. Here, we report the high-resolution crystal structure of Streptococcus pneumoniae hyaluronate lyase in the presence of HA disaccharide product, which ultimately provides the first crystallographic evidence for the binding of HA to hyaluronate lyase. This structural complex revealed a key interaction between the Streptococcus peneumoniae hyaluronate lyase protein and the product, and supports our previously proposed novel catalytic mechanism for HA degradation based on the native Streptococcus peneumoniae hyaluronate lyase structure. The information provided by this complex structure will likely be useful in the development of antimicrobial pharmaceutical agents.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: K
authors.initials: K
authors.lastname: Ponnuraj
authors.forename: M J
authors.initials: MJ
authors.lastname: Jedrzejas
mesh_terms: D001665:Binding Sites; D002118:Calcium / Q000494:pharmacology; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002384:Catalysis / Q000187:drug effects; D002808:Chondroitin Lyases / Q000737:chemistry; D018360:Crystallography, X-Ray; D004187:Disaccharides / Q000737:chemistry / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000737:chemistry / Q000378:metabolism*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011133:Polysaccharide-Lyases / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D055672:Static Electricity; D013296:Streptococcus pneumoniae / Q000201:enzymology*; D013329:Structure-Activity Relationship
chemical_list: D004187:Disaccharides; D006820:Hyaluronic Acid; D002808:Chondroitin Lyases; D011133:Polysaccharide-Lyases; C100002:hyaluronate lyase; D002118:Calcium