This article reports a targeted search for single nucleotide polymorphisms (SNPs) and functional impact characterization of human ALKBH family dioxygenases related to prostate cancer.
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This article reports a targeted search for single nucleotide polymorphisms (SNPs) and functional impact characterization of human ALKBH family dioxygenases related to prostate cancer.
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Abstract: 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 of 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.
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Walker, Alice R.; Silvestrov, Pavel; Müller, Tina A.; Podolsky, Robert H.; Dyson, Gregory; Hausinger, Robert P. et al.ALKBH7 Variant Related to Prostate Cancer Exhibits Altered Substrate Binding,
article,
February 23, 2017;
San Francisco, California.
(https://digital.library.unt.edu/ark:/67531/metadc990959/:
accessed April 27, 2024),
University of North Texas Libraries, UNT Digital Library, https://digital.library.unt.edu;
crediting UNT College of Arts and Sciences.
