Project Title

Crystallography of Inhibitor Vertebrate Lysozyme (IVY)

Presenters

Jenny WongFollow

Academic department under which the project should be listed

CSM - Chemistry and Biochemistry

Faculty Sponsor Name

Thomas Leeper

Abstract (300 words maximum)

Cryocrystallography of macromolecules features a high-resolution structure of individual atoms forming a nonsystematic lattice with internal dimensions interpreted by the diffraction of X-rays. By achieving the optimal conditions for crystal growth, a slow and controlled precipitation from the solvent creates a supersaturated environment to generate spontaneous nucleation of crystals. For this project, we are specifically targeting the protein structure of inhibitor vertebrate lysozyme (IVY) produced by Pseudomonas aeruginosa (PA). PA is an opportunistic pathogen that invades the host system during the latter stages of cystic fibrosis patients due to the weakened state of their immune system from earlier bacterial infections. PA is a virulent organism contributed from their ability to form biofilm which characterizes antibiotic resistance and protection against the lysing of the peptidoglycan cell walls by lysozyme. To combat PA, novel drug fragments are being created to inhibit the activity of IVY as well as a ‘warhead’ to bind to the active site H62 of the biofilm-producing enzyme. Early experiments utilizing crystal soaking of IVY and the ‘warhead’ in the mother liquor yielded rod clusters whereas the method of co-crystallization grew pronounced rod crystals. As a result, crystal growth of IVY and the combined ligand ‘warhead’ compound has been achieved with future experiments surrounding the optimization of conditions to produce harvestable crystals ideal for x-ray imaging. Hence, this method will help to determine the overall binding affinity of the drug fragments and ‘warhead’ with IVY as well as future advances for mapping out the electron density of the crystal structure in order to support the idea that IVY and the ‘warhead’ have indeed bound together. If so, the ligand will inhibit IVY from biofilm formation, and without this barrier, PA will be less resistant to antibiotics which ultimately allows the lysozyme to come in and attack the pathogenic bacteria.

Project Type

Poster

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Crystallography of Inhibitor Vertebrate Lysozyme (IVY)

Cryocrystallography of macromolecules features a high-resolution structure of individual atoms forming a nonsystematic lattice with internal dimensions interpreted by the diffraction of X-rays. By achieving the optimal conditions for crystal growth, a slow and controlled precipitation from the solvent creates a supersaturated environment to generate spontaneous nucleation of crystals. For this project, we are specifically targeting the protein structure of inhibitor vertebrate lysozyme (IVY) produced by Pseudomonas aeruginosa (PA). PA is an opportunistic pathogen that invades the host system during the latter stages of cystic fibrosis patients due to the weakened state of their immune system from earlier bacterial infections. PA is a virulent organism contributed from their ability to form biofilm which characterizes antibiotic resistance and protection against the lysing of the peptidoglycan cell walls by lysozyme. To combat PA, novel drug fragments are being created to inhibit the activity of IVY as well as a ‘warhead’ to bind to the active site H62 of the biofilm-producing enzyme. Early experiments utilizing crystal soaking of IVY and the ‘warhead’ in the mother liquor yielded rod clusters whereas the method of co-crystallization grew pronounced rod crystals. As a result, crystal growth of IVY and the combined ligand ‘warhead’ compound has been achieved with future experiments surrounding the optimization of conditions to produce harvestable crystals ideal for x-ray imaging. Hence, this method will help to determine the overall binding affinity of the drug fragments and ‘warhead’ with IVY as well as future advances for mapping out the electron density of the crystal structure in order to support the idea that IVY and the ‘warhead’ have indeed bound together. If so, the ligand will inhibit IVY from biofilm formation, and without this barrier, PA will be less resistant to antibiotics which ultimately allows the lysozyme to come in and attack the pathogenic bacteria.