Structural basis of hyaluronan degradation by Streptococcus pneumoniae hyaluronate lyase

AUTOR(ES)

Li, Songlin

FONTE

Oxford University Press

RESUMO

Streptococcus pneumoniae hyaluronate lyase (spnHL) is a pathogenic bacterial spreading factor and cleaves hyaluronan, an important constituent of the extra– cellular matrix of connective tissues, through an enzymatic β–elimination process, different from the hyaluronan degradation by hydrolases in animals. The mechanism of hyaluronan binding and degradation was proposed based on the 1.56 Å resolution crystal structure, substrate modeling and mutagenesis studies on spnHL. Five mutants, R243V, N349A, H399A, Y408F and N580G, were constructed and their activities confirmed our mechanism hypothesis. The important roles of Tyr408, Asn349 and His399 in enzyme catalysis were proposed, explained and confirmed by mutant studies. The remaining weak enzymatic activity of the H399A mutant, the role of the free carboxylate group on the glucuronate residue, the enzymatic behavior on chondroitin and chondroitin sulfate, and the small activity increase in the N580G mutant were explained based on this mechanism. A possible function of the C–terminal β–sheet domain is to modulate enzyme activity through binding to calcium ions.

Documentos Relacionados

• Electrophoretic Characteristics of Staphylococcal Hyaluronate Lyase
• Purification and properties of streptococcal hyaluronate lyase.
• Human argininosuccinate lyase: A structural basis for intragenic complementation
• Molecular Basis of Rifampin Resistance in Streptococcus pneumoniae
• Distribution, Genetic Diversity, and Variable Expression of the Gene Encoding Hyaluronate Lyase within the Streptococcus suis Population