8QN0

Soluble epoxide hydrolase in complex with RK3

Summary for 8QN0

• Entry DOI: 10.2210/pdb8qn0/pdb
• Related: 8QMZ
• Descriptor: Bifunctional epoxide hydrolase 2, (3~{a}~{R},6~{a}~{S})-~{N}-[(2,4-dichlorophenyl)methyl]-5-(4-methylphenyl)sulfonyl-1,3,3~{a},4,6,6~{a}-hexahydropyrrolo[3,4-c]pyrrole-2-carboxamide, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: complex, structural genomics, structural genomics consortium, sgc, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 85211.37

Authors

Kumar, A.,Zhu, F.,Ehrler, J.M.H.,Li, F.,Empel, C.,Xu, Y.,Atodiresei, I.,Koenigs, R.M.,Proschak, E.,Knapp, S.,Structural Genomics Consortium (SGC) (deposition date: 2023-09-25, release date: 2024-02-14)

Primary citation

Li, F.,Zhu, W.F.,Empel, C.,Datsenko, O.,Kumar, A.,Xu, Y.,Ehrler, J.H.M.,Atodiresei, I.,Knapp, S.,Mykhailiuk, P.K.,Proschak, E.,Koenigs, R.M.
Photosensitization enables Pauson-Khand-type reactions with nitrenes.
Science, 383:498-503, 2024

PubMed Abstract: The Pauson-Khand reaction has in the past 50 years become one of the most common cycloaddition reactions in chemistry. Coupling two unsaturated bonds with carbon monoxide, the transformation remains limited to CO as a C building block. Herein we report analogous cycloaddition reactions with nitrenes as an N unit. The reaction of a nonconjugated diene with a nitrene precursor produces bicyclic bioisosteres of common saturated heterocycles such as piperidine, morpholine, and piperazine. Experimental and computational mechanistic studies support relaying of the diradical nature of triplet nitrene into the π-system. We showcase the reaction's utility in late-stage functionalization of drug compounds and discovery of soluble epoxide hydrolase inhibitors.

PubMed: 38301027
DOI: 10.1126/science.adm8095

Experimental method

X-RAY DIFFRACTION (1.49 Å)