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Molecular Physiology & Biophysics

Derek P. Claxton, PhD

Assistant Professor, Molecular Physiology and Biophysics

Nutrient transport and metabolism in health and disease

The Claxton laboratory is interested in the molecular processes that govern nutrient transport and metabolism in health and disease. Our primary target is glucose-6-phosphatase, which catalyzes the transport and hydrolysis of the intracellular glucose intermediate glucose-6-phosphate. The function of this multi-component enzyme is critical for hepatic glucose production and fine-tuning glucose-stimulated insulin secretion from pancreatic beta cells. Dysregulation is linked to hyperglycemia in diabetes, and missense mutations that cripple enzyme activity cause glycogen storage disease. Our goal is to define the structural and mechanistic basis of transport and catalysis using an integrated structural biology/biophysics approach that combines the power of computational methods with structure determination, EPR spectroscopy and biochemistry. The laboratory has an established collaboration with the O’Brien lab.

Recent publications:

  1. Sinclair M, Stein RA, Sheehan J, Overway E, O’Brien RM, Tajkhorshid E, Claxton DP. Molecular mechanisms of functional impairment for active site mutations in glucose-6-phosphatase catalytic subunit 1 linked to glycogen storage disease type 1a. bioRxiv, 2023. DOI 10.1101/2023.03.13.532485.
  2. Overway EM, Bosma KJ, Claxton DP, Oeser JK, Singh K, Breidenbach LB, Mchaourab HS, Davis LK, O’Brien RM. Non-synonymous single nucleotide polymorphisms in the G6PC2 gene affect protein expression, enzyme activity and fasting blood glucose. Journal of Biological Chemistry, 298, 101534, 2022.
  3. Claxton DP, Overway EM, Oeser JK, O’Brien RM and Mchaourab HS. Biophysical and functional properties of purified glucose-6-phosphatase catalytic subunit 1. Journal of Biological Chemistry, 298, 101520, 2022.