Mapping the structural basis for mechanistic diversity in metalloenzyme superfamilies

Project: Research project

Description

Project Summary Enzymes that employ transition metals to initiate free-radical mechanisms require exquisite control of highly reactive intermediates. The mechanism by which diverse outcomes can be controlled by similar enzyme structures and active sites is not well understood. Global study of entire enzyme classes provides detailed, testable hypotheses about the means by which distinct outcomes are accomplished, providing deeper insight into the reactions catalyzed by individual members. This family-wide approach will be essential for controlling these scaffolds, both in engineering of new protein-based catalysts and in targeting these systems for novel antimicrobial therapeutics. This approach has already allowed for successful reengineering of non-native activity into a new scaffold using observations gleaned from structural data. Continued work to reveal the structural underpinnings of mechanism in complex metalloenzymes will enable exploitation of the seemingly limitless catalytic capabilities of these systems in the design of new drugs, new technological tools, and new chemical processes.
StatusActive
Effective start/end date8/1/165/31/21

Funding

  • National Institutes of Health: $386,431.00
  • National Institutes of Health: $376,836.00
  • National Institutes of Health: $386,202.00

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Scaffolds
Enzymes
Reengineering
Free Radicals
Transition metals
Catalysts
Pharmaceutical Preparations
Proteins