Using MOE to Investigate Potential Ligands for StarD6 — Presentation Detail — Celebration of Scholars

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Additional Information

More information is available at carthage.edu/celebration-scholars/. The following are members of the Research, Scholarship, and Creativity Committee who are eager to listen to ideas and answer questions:

Jun Wang
Kim Instenes
John Kirk
Nora Nickels
Andrew Pustina
James Ripley

Using MOE to Investigate Potential Ligands for StarD6

Name: Danielle Borchart
Major: Chemistry
Hometown: Hudson WI
Faculty Sponsor:
Other Sponsors:
Type of research: SURE
Funding: SURE

Name: Indi Conover
Major: Neuroscience
Hometown: Oakdale MN
Faculty Sponsor:
Other Sponsors:
Type of research: SURE
Funding: SURE

Name: Gabriella Papale
Department: Natural Science
Type of research: SURE
Funding: SURE

Abstract

StAR-related lipid transfer domain protein 6, or StarD6, is a member of the steroidogenic acute regulatory protein family. Previous work from Letourneau revealed the solution structure of this protein and demonstrated that StarD6 specifically binds testosterone, a steroid hormone. Molecular dynamic simulations revealed several key amino acid residues that may be involved in ligand-binding. We propose that these amino acids residues are crucial for not only the binding of testosterone, but for other known StarD6 ligands such as cholesterol and pregnanolone. Using a molecular modeling program called Molecular Operating Environment (MOE), we determined that an asparagine residue at position 191 (Asn191) not only forms a hydrogen bond with the carbonyl oxygen atom located on C3 of testosterone, but also with the carbonyl or hydroxyl oxygen at this position on other StarD6 ligands. Substitution of this residue with isoleucine (Ile), an amino acid that is incapable of forming a hydrogen bond, resulted in a lower calculated binding affinity for known StarD6 ligands. Recently, Kim correlated a single nucleotide polymorphism in the StarD6 promoter with Alzheimer’s Disease (AD). Since steroid hormones such as dehydroepiandrosterone (DHEA) and allopregnanolone are also implicated in the onset and progression of this disease, we tested the validity of these compounds as StarD6 ligands. Both ligands are predicted to bind to StarD6 in a similar fashion as testosterone, requiring formation of a hydrogen bond with Asn191.