5NAL

The crystal structure of inhibitor-15 covalently bound to PDE6D

5NAL の概要

• エントリーDOI: 10.2210/pdb5nal/pdb
• 分子名称: Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit delta, ~{N}4-[(4-chlorophenyl)methyl]-~{N}1-(cyclohexylmethyl)-~{N}4-cyclopentyl-~{N}1-[(~{Z})-4-[(~{E})-methyliminomethyl]-5-oxidanyl-hex-4-enyl]benzene-1,4-disulfonamide (3 entities in total)
• 機能のキーワード: lipid binding protein, woodward's reagent k, covalent protein labeling at glutamic acids, arl2 mediated cargo release
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm, cytosol : O43924
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18105.31

構造登録者

Fansa, E.K.,Martin-Gago, P.,Waldmann, H.,Wittinghofer, A. (登録日: 2017-02-28, 公開日: 2017-05-10, 最終更新日: 2024-10-23)

主引用文献

Martin-Gago, P.,Fansa, E.K.,Winzker, M.,Murarka, S.,Janning, P.,Schultz-Fademrecht, C.,Baumann, M.,Wittinghofer, A.,Waldmann, H.
Covalent Protein Labeling at Glutamic Acids.
Cell Chem Biol, 24:589-597.e5, 2017

PubMed Abstract: Covalent labeling of amino acids in proteins by reactive small molecules, in particular at cysteine SH and lysine NH groups, is a powerful approach to identify and characterize proteins and their functions. However, for the less-reactive carboxylic acids present in Asp and Glu, hardly any methodology is available. Employing the lipoprotein binding chaperone PDE6δ as an example, we demonstrate that incorporation of isoxazolium salts that resemble the structure and reactivity of Woodward's reagent K into protein ligands provides a novel method for selective covalent targeting of binding site carboxylic acids in whole proteomes. Covalent adduct formation occurs via rapid formation of enol esters and the covalent bond is stable even in the presence of strong nucleophiles. This new method promises to open up hitherto unexplored opportunities for chemical biology research.

PubMed: 28434875
DOI: 10.1016/j.chembiol.2017.03.015

実験手法

X-RAY DIFFRACTION (2.2 Å)