Presenter Information

Nicholas HorvathFollow

Presentation Title

Synthesis and analysis of Streptococcus pneumoniae SrtA substrate analogs

Presentation Type

Poster

Abstract

Sortases are cysteine transpeptidases found primarily on the cell surface of Gram-positive bacteria. Attempts at understanding how these enzymes recognize and bind substrates are integral to furthering their usefulness in protein engineering and, potentially, treatment of bacterial diseases. Of specific interest to us is sortase A from Streptooccus pneumoniae (SrtApneu), as it demonstrates a broad substrate tolerance not observed in other sortase A homologs. With this in mind, we have begun work towards crystallizing SrtApneu with a bound substrate analog. Initial work with a modified peptide substrate has demonstrated the ability for ketone substituted peptides to function as viable inhibitors of SrtApneu. Recently, efforts towards synthesizing a solid-phase peptide synthesis ready ketomethylene-linked “dipeptide” have been successful, however, its insertion in place of the scissile peptide bond of a known SrtApneu substrate has yet to be demonstrated. Key words: sortase, substrates, inhibitors, protein engineering

Start Date

10-5-2018 12:00 PM

End Date

10-5-2018 2:00 PM

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May 10th, 12:00 PM May 10th, 2:00 PM

Synthesis and analysis of Streptococcus pneumoniae SrtA substrate analogs

Sortases are cysteine transpeptidases found primarily on the cell surface of Gram-positive bacteria. Attempts at understanding how these enzymes recognize and bind substrates are integral to furthering their usefulness in protein engineering and, potentially, treatment of bacterial diseases. Of specific interest to us is sortase A from Streptooccus pneumoniae (SrtApneu), as it demonstrates a broad substrate tolerance not observed in other sortase A homologs. With this in mind, we have begun work towards crystallizing SrtApneu with a bound substrate analog. Initial work with a modified peptide substrate has demonstrated the ability for ketone substituted peptides to function as viable inhibitors of SrtApneu. Recently, efforts towards synthesizing a solid-phase peptide synthesis ready ketomethylene-linked “dipeptide” have been successful, however, its insertion in place of the scissile peptide bond of a known SrtApneu substrate has yet to be demonstrated. Key words: sortase, substrates, inhibitors, protein engineering