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Cryo-EM of Metabolic Enzymes for Drug Design


EMSL Project ID
51281

Abstract

Given the high failure rate of drug candidates that enter clinical trials and the length of time involved, there is an urgent need to develop new approaches to lower failure rates. Some of the reasons for failure derive from ineffective targeting of the relevant disease-linked proteins in their physiological, native states, in addition to toxic side-effects from off-target reactions. The hypothesis underlying our approach is that by better characterization of the native structure and multiple conformational states of key disease-linked proteins, we will be more successful at targeting, reducing the cost and time for discovering new drugs. Atomic resolution cryo-EM is uniquely positioned to provide this kind of information. This proposal is aimed at establishing a platform for drug discovery for targeting key metabolic enzymes that underlie many diseases ranging from cancer to infectious diseases with cryo-EM.

Project Details

Start Date
2020-02-15
End Date
2021-03-17
Status
Closed

Team

Principal Investigator

Sriram Subramaniam
Institution
The University of British Columbia

Team Members

Shanti Swaroop Srivastava
Institution
The University of British Columbia

Alison Berezuk
Institution
The University of British Columbia

Xing Zhu
Institution
The University of British Columbia

Sagar Chittori
Institution
The University of British Columbia

Theo Humphreys
Institution
Oregon Health & Science University