Enzymes as Drug Targets in the Isoprenoid Biosynthesis Pathway: Structure, Mechanism and Inhibition

Enzymes in isoprenoid biosynthesis pathway play important roles in all living organisms. Several of them have been identified as drug targets. Here we reported the inhibition study of isopentenyl diphosphate/dimethylallyl diphosphate isomerase (IPPI) and deoxyzylolus reductoisomerase (DXR), along with crystal structures of enzyme inhibitor complexes. A high throughput screening method was developed, by which novel potent inhibitors against farnesyl diphosphate synthase (FPPS) and Staph. Aureus dehydrosqulene synthase (CrtM) were identified. We also conducted thermodynamic study of FPPS inhibition, which revealed that both enthalpy and antropy driven binding inhibitors have similar activity.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biophysics and Computational Biology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Yin, Fenglin

Contributors dc:contributor

• Oldfield, Eric

• Chemistry, Biochemistry

Language dc:language

eng

Identifier

(MiAaPQ)AAI3314948

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/85468