ALKBH7 Variant Related to Prostate Cancer Exhibits Altered Substrate Binding

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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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13 p.

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Walker, Alice R.; Silvestrov, Pavel; Müller, Tina A.; Podolsky, Robert H.; Dyson, Gregory; Hausinger, Robert P. et al. February 23, 2017.

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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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13 p.

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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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  • PLOS Computational Biology, 2017. San Francisco, CA: Public Library of Science

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  • Publication Title: PLOS Computational Biology
  • Volume: 13
  • Issue: 2
  • Pages: 1-13
  • Peer Reviewed: Yes

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UNT Scholarly Works

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  • September 23, 2016

Accepted Date

  • January 4, 2017

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  • February 23, 2017

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  • Aug. 29, 2017, 9:38 a.m.

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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. (digital.library.unt.edu/ark:/67531/metadc990959/: accessed November 18, 2018), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT College of Arts and Sciences.