“Wow, sarcasm! That’s original!” -Dr. Horrible
Alice is currently a graduate student in the Cisneros research group at Wayne State. She is a physical chemist, with a focus on computational biochemistry, especially focusing on cancer-related problems. Prior to her work at Wayne, she obtained her B.S. in Chemistry from the University of Michigan-Dearborn and worked in industry for several years. She enjoys knitting, video games, and building computers in her spare time.
ALKBH7 Variant Related to Prostate Cancer Exhibits Altered Substrate Binding
The search for prostate cancer biomarkers has received increased attention, and several DNA repair related enzymes have been linked to this dysfunction. Here we report a targeted search for single nucleotide polymorphisms (SNPs) and functional impact characterization of human ALKBH family dioxygenases related to prostate cancer. Our results uncovered a SNP on ALKBH7, rs7540, which is associated with prostate cancer disease in a statistically significantly manner in two separate cohorts, and maintained in African American men. Comparisons of molecular dynamics (MD) simulations on the wild-type and variant protein structures indicate that the resulting alteration in the enzyme induces a significant structural change that reduces ALKBH7’s ability to bind its cosubstrate. Experimental spectroscopy studies with purified proteins validate our MD predictions and corroborate the conclusion that this cancer-associated mutation affects productive cosubstrate binding in ALKBH7.