1lxk
From Proteopedia
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Streptococcus pneumoniae Hyaluronate Lyase in Complex with Tetrasaccharide Hyaluronan Substrate
Overview
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-A 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 Tyr(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.
About this Structure
1LXK is a Single protein structure of sequence from Streptococcus pneumoniae. Active as Hyaluronate lyase, with EC number 4.2.2.1 Full crystallographic information is available from OCA.
Reference
Mechanism of hyaluronan degradation by Streptococcus pneumoniae hyaluronate lyase. Structures of complexes with the substrate., Jedrzejas MJ, Mello LV, de Groot BL, Li S, J Biol Chem. 2002 Aug 2;277(31):28287-97. Epub 2002 May 3. PMID:11991948
Page seeded by OCA on Tue Nov 20 20:58:00 2007
