From Structure to Motion: Studying the Conformational Changes of Human NTHL1
Ngo, Marcos
Ngo, Marcos
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Abstract
Human endonuclease III-like protein 1 (hNTHL1) is a base excision repair protein responsible for the removal of oxidized pyrimidines. Mutations in hNTHL1 are linked to colorectal and breast cancer, making structural characterization critical. This project aims to characterize the structure and conformational changes of hNTHL1 through X-ray crystallography and molecular dynamics (MD) simulations. Previously, this enzyme was solved in an unexpected open conformation, suggesting that it must adopt a closed conformation upon binding to DNA to assemble its active site. However, recently solved crystal structures of a disease-associated variant adopted a closed conformation, and a ligand-induced intermediate state was observed. MD simulations across these conformations reveal that hNTHL1 samples both open and closed states. These results suggest that the enzyme can interconvert between conformations without binding to DNA, and that disease-associated mutations can shift the conformational landscape.
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Date
1/1/2026
Student Status
Senior (Graduating in 2026)
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Poster
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Chemistry
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College of Arts and Sciences
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Physical Science