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Characterization of hyaluronic acid specific hyaluronate lyase (HylP) from Streptococcus pyogenes

IR@CDRI: CSIR-Central Drug Research Institute, Lucknow


Field	Value

Creator	Singh, S K Malhotra, Soniya Akhtar, M S

Date	2014-08-12T04:32:16Z 2014-08-12T04:32:16Z 2014

Identifier	Biochimie, 2014, 102, 203-10 http://hdl.handle.net/123456789/1357

Description	Streptococcus pyogenes is associated with a wide variety of mucosal and invasive infections that claim human life. The conversion from non pathogenic to toxigenic strain of S. pyogenes are thought to be mediated by bacteriophage infection in several cases. The hyaluronic acid (HA) degrading enzyme Hyaluronate lyase (HL) is proposed to be one of the key bacteriophage-encoded virulence factors. In the present work, HL of S. Pyogenes bacteriophage H4489A (HylP) was expressed in E. coli, purified and their structural and functional properties were studied. The enzyme exists in an extended trimeric conformation whose function is influenced by calcium ions. The collagenous Gly-X-Y motif of the enzyme influences stability and interact with calcium ions suggesting its role in the enzyme regulation The HylP shows sequential unfolding through the N - terminal domain. The primary catalytic residues of the enzyme seem to be in the first pocket consisting of Asp170 and Tyr182; however the enzyme activity is considerably reduced with mutation in the second pocket consisting of Glu295 and Tyr298. The catalytic residues span between the regions containing 135-308 amino acids where both the catalytic pocket has a prominent positively charged residue. The net positive potential of the cleft may help in recruiting the negatively charged polymeric HA. Interestingly, unlike other phage HLs, HylP is inhibited by L-ascorbate through non competitive manner.

Format	903045 bytes application/pdf

Language	en

Relation	CSIR-CDRI Communication No. 8651

Subject	Hyaluronic Acid Hyaluronate Lyase Enzyme Catalysis Bacteriophage

Title	Characterization of hyaluronic acid specific hyaluronate lyase (HylP) from Streptococcus pyogenes

Type	Article