Research Project
Grant-in-Aid for Scientific Research (C)
BLT1 is a high affinity G-protein coupled receptor (GPCR) for leukotriene B4 (LTB4) and involved in the activation and chemotaxis of leukocytes. In this study, we succeeded in the structural analysis of the complex of BLT1 and the inverse agonist, BIIL260. The benzamidine moiety of BIIL260 bound to the binding pocket of the sodium ion and water cluster and stabilized the inactivate state of GPCR. As the residues involved in the benzamidine binding are widely conserved among many GPCRs, the present structure will enable the rational development of inverse agonists specific for each GPCR.
Gタンパク質共役型受容体(GPCR)は、哺乳類において最大の遺伝子ファミリーを形成し、現在用いられている薬剤の3分の1がGPCRを標的としている。したがって、GPCRの活性を抑制する拮抗薬(インバースアゴニスト)の開発は創薬に直結する。本研究によって、GPCRの拮抗薬を理論的に設計することが可能となり、GPCRを標的とした創薬研究が飛躍的に進展することが期待される。
All 2020 2019 2018 2017 2016 Other
All Int'l Joint Research (2 results) Journal Article (25 results) (of which Int'l Joint Research: 12 results, Peer Reviewed: 25 results, Open Access: 19 results, Acknowledgement Compliant: 5 results) Presentation (36 results) (of which Int'l Joint Research: 24 results) Remarks (4 results)
Biochemical and Biophysical Research Communications
Volume: In press Issue: 4 Pages: 909-914
10.1016/j.bbrc.2020.03.037
Genes Cells.
Volume: 25(3) Issue: 3 Pages: 197-214
10.1111/gtc.12750
120006873037
Org Lett
Volume: 21 Issue: 12 Pages: 4667-4670
10.1021/acs.orglett.9b01554
Allergy
Volume: 印刷中 Issue: 11 Pages: 2237-2240
10.1111/all.13831
FASEB J
Volume: 33 Issue: 11 Pages: 12668-12679
10.1096/fj.201901360r
J Dermatol Sci
Volume: 95 Issue: 3 Pages: 130-133
10.1016/j.jdermsci.2019.07.010
Int J Mol Sci
Volume: 20 Issue: 14 Pages: 3580-3580
10.3390/ijms20143580
Cutting-Edge Organic Synthesis and Chemical Biology of Bioactive Molecules
Volume: 1 Pages: 233-246
10.1007/978-981-13-6244-6_10
Volume: 33 Issue: 3 Pages: 3392-3403
10.1096/fj.201801805r
Nature Chemical Biology
Volume: 14 Issue: 3 Pages: 262-269
10.1038/nchembio.2547
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
Volume: 印刷中 Issue: 6 Pages: R892-R901
10.1152/ajpregu.00371.2017
Biochem Biophys Res Commun
Volume: 504 Issue: 3 Pages: 562-568
10.1016/j.bbrc.2018.06.026
Journal of Lipid Research
Volume: 59 Issue: 3 Pages: 542-549
10.1194/jlr.m083030
JCI Insight
Volume: 3 Issue: 18 Pages: 96902-96902
10.1172/jci.insight.96902
Inflamm Regen
Volume: 38 Issue: 1 Pages: 29-29
10.1186/s41232-018-0087-4
Acta Paediatrica
Volume: 107 Issue: 1 Pages: 95-100
10.1111/apa.14068
Scientific Reports
Volume: 7 Issue: 1 Pages: 13267-13267
10.1038/s41598-017-13122-8
PLoS One
Volume: 12 Issue: 9 Pages: 0185133-0185133
10.1371/journal.pone.0185133
Analytical Chemistry
Volume: 89 Issue: 16 Pages: 8545-8553
10.1021/acs.analchem.7b02375
Volume: 486 Issue: 4 Pages: 1077-1082
10.1016/j.bbrc.2017.03.165
Volume: 31 Issue: 4 Pages: 1584-1594
10.1096/fj.201601095r
Toxicol Sci
Volume: in press Pages: 402-411
10.1093/toxsci/kfw261
Volume: 30 Issue: 5 Pages: 1811-1822
10.1096/fj.201500117
Volume: 30 Issue: 2 Pages: 933-947
10.1096/fj.15-279653
Sci Rep
Volume: 6 Issue: 1 Pages: 34560-34560
10.1038/srep34560
http://plaza.umin.ac.jp/j_bio/publication.html
http://researchmap.jp/toshiakiokuno