Abstract
Glutathione S‐transferases (GSTs) are a family of phase II metabolic enzymes. These enzymes catalyze the conjugation of glutathione (GSH) to xenobiotic substrates for detoxification. There is evidence that supports the role of GSTπ in cancer development. Ezatiostat (EZT) has received orphan drug status for Myelodysplastic Syndrome (MDS). A single nucleotide polymorphism (SNP) Ile105Val (I105V) near the Glutathione binding site of GSTπ affects its structure, and this may cause chemotherapeutic resistance. We hypothesize that this mutation expressed in some individuals may cause resistance to EZT. This study incorporates computational analysis of the binding mode for EZT with wild‐type and I105V. We used residue scanning and molecular dynamics (MD) to compare the interactions for EZT. Results from MD show differences in the EZT binding mode in wildtype and I105V GST. GST with the I105V mutation makes less interactions with EZT. Future work involves inhibition assays and x‐ray crystallography to validate the computational results.Support or Funding InformationDean's Internal Research Support GrantThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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