Student Summer Scholars Manuscripts
 

First Advisor

Paul Cook

Keywords

Bacillithiol, BrxA, BrxB, X-ray Crystallography, low molecular weight thiol, gram-positive, Staphylococcus aureus

Disciplines

Chemistry

Included in

Chemistry Commons

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Abstract

Bacillithiol is an important compound involved in intracellular redox homeostasis and fosfomycin resistance mechanisms of some Gram-positive bacterial pathogens. Cellular regeneration of active bacillithiol (BSH) from a disulfide (BSSB) or mixed disulfide state (BSS-Protein) involves the bacilliredoxin enzymes BrxA/B. An X-ray crystallographic structure of apo BrxA from Bacillus subtilis has been previously characterized, but no BrxB or BSSB-bound Brx structure currently exists. Here we present an X-ray crystallographic structure of BrxA from the pathogen Staphylococcus aureus with a bacillithiol disulfide (BSSB) bound in the active site. Elucidation of this structure will help researchers to understand how BSSB binds in bacilliredoxins, and provide insight into the Brx catalytic mechanism. Functional activity of YpdA, another enzyme involved in BSH regeneration, is also investigated.