6RCY

CRYSTAL STRUCTURE OF FK1 DOMAIN OF FKBP52 IN COMPLEX WITH A BIO-INSPIRED HYBRID FLUORESCENT LIGAND

6RCY の概要

• エントリーDOI: 10.2210/pdb6rcy/pdb
• 分子名称: Peptidyl-prolyl cis-trans isomerase FKBP4, (2~{S})-5-carbamimidamido-2-[[(2~{S})-2-[[(2~{S})-1-[5-(dimethylamino)naphthalen-1-yl]sulfonylpiperidin-2-yl]carbonylamino]-4-phenyl-butanoyl]amino]pentanoic acid (3 entities in total)
• 機能のキーワード: fkbp52, the n-terminal domain, isomerase, ligand, fluorescence
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16905.18

構造登録者

Li de la Sierra-Gallay, I.,Byrne, C. (登録日: 2019-04-12, 公開日: 2020-05-13, 最終更新日: 2024-01-24)

主引用文献

de la Sierra-Gallay, I.L.,Belnou, M.,Chambraud, B.,Genet, M.,van Tilbeurgh, H.,Aumont-Nicaise, M.,Desmadril, M.,Baulieu, E.E.,Jacquot, Y.,Byrne, C.
Bioinspired Hybrid Fluorescent Ligands for the FK1 Domain of FKBP52.
J.Med.Chem., 63:10330-10338, 2020

PubMed Abstract: The protein FKBP52 is a steroid hormone receptor coactivator likely involved in neurodegenerative disease. A series of small, water-soluble, bioinspired, pseudopeptidic fluorescent ligands for the FK1 domain of this protein are described. The design is such that engulfing of the ligand in the pocket of this domain is accompanied by hydrogen-bonding of the dansyl chromophore which functions as both an integral part of the ligand and a fluorescent reporter. Binding is concomitant with a significant wavelength shift and an enhancement of the ligand fluorescence signal. Excitation of FK1 domain native tryptophan residues in the presence of bound ligand results in Förster resonance energy transfer. Variation of key ligand residues within the short sequence was undertaken, and the interaction of the resulting library with the protein was measured by techniques including isothermal calorimetry analysis, fluorescence, and FRET quenching, and a range of values were determined. Cocrystallization of a protein ligand complex at 2.30 Å resolution provided detailed information at the atomic scale, while also providing insight into native substrate binding.

PubMed: 32866001
DOI: 10.1021/acs.jmedchem.0c00825

実験手法

X-RAY DIFFRACTION (2.3 Å)