Structural Studies of Enzymes Involved in Drug Resistance and Antibiotic Biosynthesis

The emergence of pathogenic bacteria resistant to the current battery of effective antibiotics remains a global health concern. Antibiotic resistance genes are plasmid borne and can easily be transferred between pathogens, regardless of phylogeny. The macrolide antibiotic erythromycin can be enzymatically degraded by strains carrying the ereB locus that codes for erythromycin esterase type B and confers high level resistance to this widely used antibiotic. We have determined high resolution crystal structures of apo-EreB, EreB bound to its final product and an inactive EreB variant bound to the substrate erythromycin. In addition, we also performed biochemical studies on EreB such as HPLC tracing of erythromycin degradation, agar plate based bioassay and enzyme-substrate affinity based on isothermal titration calorimetry. Our structural and biochemical data helps to characterize EreB and elucidate its catalytic mechanism, providing a valuable framework to develop efficient inhibitors of EreB for pharmaceutical application.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biochemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2014

Author dc:creator

• Zou, Yaozhong

Contributors dc:contributor

• Nair, Satish K.

• Chemistry, Biochemistry

Identifier

(UMI)AAI3337992

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/72338