Structural characterization of glycyl radical enzymes in the human gut microbiome

Anaerobic bacteria play important roles in the human gut microbiome and have dedicated chemical pathways for growth in the absence of oxygen. Glycyl radical enzymes (GREs) use an oxygen-sensitive glycyl radical cofactor to perform challenging, radical-based chemistry. Generation of this cofactor requires a dedicated GRE-activating enzyme (GRE-AE). This thesis presents structural analysis of one GRE involved in sulfur metabolism, structural and biochemical analysis of another GRE involved in nucleotide metabolism, and efforts towards structural characterization of a GRE-AE. C-S bond cleavage of isethionate by the GRE isethionate sulfite-lyase (IslA) generates sulfite, a substrate for sulfite respiration that in turn produces the disease-associated metabolite hydrogen sulfide. In this thesis, I present and describe an X-ray crystal structure of IslA from Bilophila wadsworthia with isethionate bound.

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Biology

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2020

Author dc:creator

• Dawson, Christopher Daniel.

Advisor dc:contributor.advisor

• Catherine L. Drennan.

• Biology.

Statement dc:rights

• MIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided.

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/1721.1/127128

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/127128