Genome-based identification of a carbohydrate binding module in Streptococcus pneumoniae hyaluronate lyase.
Hyaluronate lyase enzymes degrade hyaluronan, the main polysaccharide component of the connective tissues of higher animals, thereby destroying the normal connective tissue structure and exposing the host tissue cells to various endo- and exogenous factors, including bacterial toxins. The 3D crystal structures of functionally active but truncated Streptococcus pneumoniae and S. agalactiae hyaluronate lyases, along with their substrate and product complexes, have been determined. The enzymes are multidomain proteins with helical barrel-like catalytic domains and two types of beta-sheet domains. Here, through genome-based bioinformatics studies we identify an additional beta-sheet domain present in the most N-terminal part of streptococcal hyaluronate lyases. Fold recognition and modeling studies show that the domain is structurally similar to carbohydrate binding modules and is therefore likely to be directly involved in hyaluronan binding. Likely carbohydrate binding residues were identified and electrostatic complementarity of the hyaluronate lyase domain with hyaluronan demonstrated. The newly identified presumed hyaluronan binding domain likely improves catalytic efficiency by colocalizing the enzyme and its substrate. Other possible functions are discussed. Two contacting aromatic residues are conserved in the hydrophobic core of the hyaluronate lyase domain and in many, perhaps all, families in the superfamily in which they may be placed. This observation may help the identification and classification of other carbohydrate binding modules.
Rigden
Daniel J
DJ
Embrapa Genetic Resources and Biotechnology, Cenargen/Embrapa, Brasilia-DF, Brazil. daniel@cenargen.embrapa.br
Jedrzejas
Mark J
MJ
D000595:Amino Acid Sequence; D001665:Binding Sites; D050260:Carbohydrate Metabolism; D002241:Carbohydrates / Q000737:chemistry; D019295:Computational Biology / Q000379:methods; D016680:Genome, Bacterial; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011133:Polysaccharide-Lyases / Q000737:chemistry* / Q000378:metabolism*; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013296:Streptococcus pneumoniae / Q000201:enzymology*
D002241:Carbohydrates; D011133:Polysaccharide-Lyases; C100002:hyaluronate lyase