Event Title

Two Mutations Are Necessary to Convert Class D Beta-lactamase Function to Beta-lactam Sensor Function

Presentation Type

Poster/Portfolio

Presenter Major(s)

Chemistry, Biology

Mentor Information

David Leonard

Department

Chemistry

Location

Henry Hall Atrium 74

Start Date

10-4-2013 10:00 AM

End Date

10-4-2013 11:00 AM

Keywords

Health, Life Science

Abstract

Class D beta-lactamases and beta-lactam sensors share common topological folds and a similar acylation mechanism. The difference between these proteins lie in Class D beta-lactamases' ability to deacylate the substrate, allowing the them to turn over substrate at an astonishing rate. The beta-lactam sensors on the other hand are unable to complete catalysis. Other studies have implicated specific neutral polar residues play a role in the sensors' inability to deacylate bound substrate. With two key active site mutations to Class D beta-lactamase OXA-24, we caused a dramatic drop in ampicillin hydrolysis, suggesting that these two residues alone may be responsible for the functional difference of these two proteins. X-ray crystallographic analysis reveals that an active site water in OXA-24 is missing in the double mutant, providing a possible explanation for the destabilization of the carboxylysine in beta-lactam sensors.

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Apr 10th, 10:00 AM Apr 10th, 11:00 AM

Two Mutations Are Necessary to Convert Class D Beta-lactamase Function to Beta-lactam Sensor Function

Henry Hall Atrium 74

Class D beta-lactamases and beta-lactam sensors share common topological folds and a similar acylation mechanism. The difference between these proteins lie in Class D beta-lactamases' ability to deacylate the substrate, allowing the them to turn over substrate at an astonishing rate. The beta-lactam sensors on the other hand are unable to complete catalysis. Other studies have implicated specific neutral polar residues play a role in the sensors' inability to deacylate bound substrate. With two key active site mutations to Class D beta-lactamase OXA-24, we caused a dramatic drop in ampicillin hydrolysis, suggesting that these two residues alone may be responsible for the functional difference of these two proteins. X-ray crystallographic analysis reveals that an active site water in OXA-24 is missing in the double mutant, providing a possible explanation for the destabilization of the carboxylysine in beta-lactam sensors.