6M9T

Crystal structure of EP3 receptor bound to misoprostol-FA

6M9T の概要

• エントリーDOI: 10.2210/pdb6m9t/pdb
• 分子名称: Prostaglandin E2 receptor EP3 subtype, Endolysin chimera, (11alpha,12alpha,13E,16S)-11,16-dihydroxy-16-methyl-9-oxoprost-13-en-1-oic acid, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: gpcr, prostaglandin e2 receptor 3 (ep3), prostaglandin analogue, membrane protein, misoprostol-fa (biologically active free acid), xfel, lcp, t4l
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 62262.59

構造登録者

Audet, M.,White, K.L.,Breton, B.,Zarzycka, B.,Han, G.W.,Lu, Y.,Gati, C.,Batyuk, A.,Popov, P.,Velasquez, J.,Manahan, D.,Hu, H.,Weierstall, U.,Liu, W.,Shui, W.,Katrich, V.,Cherezov, V.,Hanson, M.A.,Stevens, R.C. (登録日: 2018-08-24, 公開日: 2018-12-05, 最終更新日: 2024-11-06)

主引用文献

Audet, M.,White, K.L.,Breton, B.,Zarzycka, B.,Han, G.W.,Lu, Y.,Gati, C.,Batyuk, A.,Popov, P.,Velasquez, J.,Manahan, D.,Hu, H.,Weierstall, U.,Liu, W.,Shui, W.,Katritch, V.,Cherezov, V.,Hanson, M.A.,Stevens, R.C.
Crystal structure of misoprostol bound to the labor inducer prostaglandin E2receptor.
Nat. Chem. Biol., 15:11-17, 2019

PubMed Abstract: Misoprostol is a life-saving drug in many developing countries for women at risk of post-partum hemorrhaging owing to its affordability, stability, ease of administration and clinical efficacy. However, misoprostol lacks receptor and tissue selectivities, and thus its use is accompanied by a number of serious side effects. The development of pharmacological agents combining the advantages of misoprostol with improved selectivity is hindered by the absence of atomic details of misoprostol action in labor induction. Here, we present the 2.5 Å resolution crystal structure of misoprostol free-acid form bound to the myometrium labor-inducing prostaglandin E receptor 3 (EP3). The active state structure reveals a completely enclosed binding pocket containing a structured water molecule that coordinates misoprostol's ring structure. Modeling of selective agonists in the EP3 structure reveals rationales for selectivity. These findings will provide the basis for the next generation of uterotonic drugs that will be suitable for administration in low resource settings.

PubMed: 30510194
DOI: 10.1038/s41589-018-0160-y

実験手法

X-RAY DIFFRACTION (2.5 Å)