Structural insights into conformationally-gated reactions catalyzed by thiamine pyrophosphate-dependent enzymes

Thiamine pyrophosphate (TPP)-dependent enzymes utilize TPP as a biological carbanion to initiate reactions on substrates with carbonyl carbon(s), such as pyruvate and 2-oxoglutarate, two central metabolites. This thesis presents structural analyses of three TPP-dependent enzymes. Most interestingly, each mechanism of three proteins studied contains a gated step that is drastically accelerated by 3-5 orders of magnitudes through conformational changes. 1-deoxy-D-xylulose 5-phosphate (DXP) synthase catalyzes the conversion of pyruvate and D-glyceraldehyde 3-phosphate (D-GAP or G3P) into DXP, an essential precursor of isoprenoids, vitamin B1, and vitamin B6 (pyridoxal phosphate, PLP) in bacterial pathogens. Human adapts different pathways to access those essential metabolites; thus, selective inhibition of DXP synthase has been considered to be a possible approach for antibiotic therapies.

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Chemistry

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2019

Author dc:creator

• Chen, Yang-Ting(Percival Yang Ting)

Advisor dc:contributor.advisor

• Catherine L. Drennan.

• Chemistry.

Statement dc:rights

• MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/122450

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/122450