Small molecule inhibitors of 15-PGDH exploit a physiologic induced-fit closing system

Wei Huang; Hongyun Li; Janna Kiselar; Stephen P. Fink; Sagar Regmi; Alexander Day; Yiyuan Yuan; Mark Chance; Joseph M. Ready; Sanford D. Markowitz; Derek J. Taylor

doi:10.1038/s41467-023-36463-7

Nature Communications (Feb 2023)

Small molecule inhibitors of 15-PGDH exploit a physiologic induced-fit closing system

Wei Huang,
Hongyun Li,
Janna Kiselar,
Stephen P. Fink,
Sagar Regmi,
Alexander Day,
Yiyuan Yuan,
Mark Chance,
Joseph M. Ready,
Sanford D. Markowitz,
Derek J. Taylor

Affiliations

Wei Huang: Department of Pharmacology, Case Western Reserve University
Hongyun Li: Department of Medicine, Case Western Reserve University
Janna Kiselar: Department of Nutrition, Case Western Reserve University
Stephen P. Fink: Department of Medicine, Case Western Reserve University
Sagar Regmi: Department of Pharmacology, Case Western Reserve University
Alexander Day: Department of Pharmacology, Case Western Reserve University
Yiyuan Yuan: Department of Medicine, Case Western Reserve University
Mark Chance: Department of Nutrition, Case Western Reserve University
Joseph M. Ready: Department of Biochemistry, University of Texas Southwestern Medical Center
Sanford D. Markowitz: Department of Medicine, Case Western Reserve University
Derek J. Taylor: Department of Pharmacology, Case Western Reserve University

DOI: https://doi.org/10.1038/s41467-023-36463-7
Journal volume & issue: Vol. 14, no. 1
pp. 1 – 13

Abstract

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Inhibition of 15-prostaglandin dehydrogenase (15-PGDH) is a promising therapeutic target for regenerative medicine. We report the structure of 15-PGDH in complex with two different inhibitors. Unexpectedly, access to the binding pocket is regulated by a dynamic “lid” of the enzyme.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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