Sep 5, 2023
Graduate School of Agriculture research featured on the front cover of “The FEBS Journal”
A research group led by Professor Takashi Inui of the Graduate School of Agriculture along with Yuya Miyamoto (Ph.D., 2012) and Masatoshi Nakatsuji (Ph.D., 2018) from the Graduate School of Life and Environmental Sciences, Osaka Prefecture University, has published a paper titled "Structural and interaction analysis of human lipocalin-type prostaglandin D synthase with the poorly water-soluble drug NBQX" in The FEBS Journal, an international journal published by Wiley. This paper was also featured on the cover of the August 2023 issue (Volume 290, Issue 16) of The FEBS Journal.
Lipocalin-type prostaglandin D synthase (L-PGDS), a secretory transport protein, is abundantly expressed in the central nervous system of mammals and binds a variety of small hydrophobic molecules. By utilizing L-PGDS, the research group attempted to solubilize drugs that are difficult to dissolve in water and adapt them to drug delivery systems that target tissues such as cancer. So far, however, the binding mechanism of L-PGDS to drugs remains unclear.
In this study, the researchers determined the solution structure of human L-PGDS and investigated the binding mode of L-PGDS with a poorly water-soluble drug, NBQX. As a result, NMR analysis and singular value decomposition analysis revealed that two NBQX molecules bind to L-PGDS. Furthermore, molecular docking simulations revealed that L-PGDS binds two molecules of NBQX in a site known as the β-barrel interior. These findings provide new insights into the structural biology of the complex of poorly water-soluble drugs with human L-PGDS as a drug carrier.
Professor Inui explained, “Though it took some time to complete this paper, it was completed through joint research by Dr. Miyamoto and Dr. Nakatsuji, two cross-generational researchers from our lab. This is an important paper that elucidates for the first time, the binding mode of human L-PGDS to drugs.” He further added, “Dr. Miyamoto also designed the graphic on the cover page. It's pretty cool, isn't it?”
Journal: The FEBS Journal
Title: Structural and interaction analysis of human lipocalin-type prostaglandin D synthase with the poorly water-soluble drug NBQX
Author: Yuya Miyamoto, Masatoshi Nakatsuji, Takuya Yoshida, Tadayasu Ohkubo, Takashi Inui
Laboratory of Biomolecular Functional Science: https://www.biosci.osakafu-u.ac.jp/biol-macromol/home/
Graduate School of Agriculture, Osaka Metropolitan University
Professor Takashi Inui
E-mail: inuit [at]omu.ac.jp
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