1lxm
Crystal Structure of Streptococcus agalactiae Hyaluronate Lyase Complexed with Hexasaccharide Unit of Hyaluronan
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OverviewOverview
Streptococcus agalactiae hyaluronate lyase degrades primarily hyaluronan, the main polysaccharide component of the host connective tissues, into, unsaturated disaccharide units as the end product. Such function of the, enzyme destroys the normal connective tissue structure of the host and, exposes the tissue cells to various bacterial toxins. The crystal, structure of hexasaccharide hyaluronan complex with the S. agalactiae, hyaluronate lyase was determined at 2.2 A resolution; the mechanism of the, catalytic process, including the identification of specific residues, involved in the degradation of hyaluronan, was clearly identified. The, enzyme is composed structurally and functionally from two distinct, domains, an alpha-helical alpha-domain and a beta-sheet beta-domain. The, flexibility of the protein was investigated by comparing the crystal, structures of the S. agalactiae and the Streptococcus pneumoniae enzymes, and by using essential dynamics analyses of CONCOORD computer simulations., These revealed important modes of flexibility, which could be related to, the protein function. First, a rotation/twist of the alpha-domain relative, to the beta-domain is potentially related to the mechanism of processivity, of the enzyme; this twist motion likely facilitates shifting of the ligand, along the catalytic site cleft in order to reposition it to be ready for, further cleavage. Second, a movement of the alpha- and beta-domains with, respect to each other was found to contribute to a change in electrostatic, characteristics of the enzyme and appears to facilitate binding of the, negatively charged hyaluronan ligand. Third, an opening/closing of the, substrate binding cleft brings a catalytic histidine closer to the, cleavable substrate beta1,4-glycosidic bond. This opening/closing mode, also reflects the main conformational difference between the crystal, structures of the S. agalactiae and the S. pneumoniae hyaluronate lyases.
About this StructureAbout this Structure
1LXM is a Single protein structure of sequence from Streptococcus agalactiae. Active as Hyaluronate lyase, with EC number 4.2.2.1 Full crystallographic information is available from OCA.
ReferenceReference
Structure and flexibility of Streptococcus agalactiae hyaluronate lyase complex with its substrate. Insights into the mechanism of processive degradation of hyaluronan., Mello LV, De Groot BL, Li S, Jedrzejas MJ, J Biol Chem. 2002 Sep 27;277(39):36678-88. Epub 2002 Jul 18. PMID:12130645
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