7RY5

Cellular Retinoic Acid Binding Protein II with Bound Inhibitor 4-[6-({4-[(fluorosulfonyl)oxy]phenyl}ethynyl)-4,4-dimethyl-3,4-dihydroquinolin-1(2H)-yl]-4-oxobutanoic acid

This is a non-PDB format compatible entry.

Summary for 7RY5

• Entry DOI: 10.2210/pdb7ry5/pdb
• Related: 6HKR
• Descriptor: Cellular retinoic acid-binding protein 2, 4-[6-({4-[(fluorosulfonyl)oxy]phenyl}ethynyl)-4,4-dimethyl-3,4-dihydroquinolin-1(2H)-yl]-4-oxobutanoic acid (3 entities in total)
• Functional Keywords: inhibitor complex, signaling protein-inhibitor complex, signaling protein/inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 35706.55

Authors

Kimmel, B.R.,Mrksich, M. (deposition date: 2021-08-24, release date: 2021-12-15, Last modification date: 2024-11-06)

Primary citation

Kimmel, B.R.,Mrksich, M.
Development of an Enzyme-Inhibitor Reaction Using Cellular Retinoic Acid Binding Protein II for One-Pot Megamolecule Assembly.
Chemistry, 27:17843-17848, 2021

PubMed Abstract: This paper presents an enzyme building block for the assembly of megamolecules. The system is based on the inhibition of the human-derived cellular retinoic acid binding protein II (CRABP2) domain. We synthesized a synthetic retinoid bearing an arylfluorosulfate group, which uses sulfur fluoride exchange click chemistry to covalently inhibit CRABP2. We conjugated both the inhibitor and a fluorescein tag to an oligo(ethylene glycol) backbone and measured a second-order rate constant for the protein inhibition reaction of approximately 3,600 M s . We used this new enzyme-inhibitor pair to assemble multi-protein structures in one-pot reactions using three orthogonal assembly chemistries to demonstrate exact control over the placement of protein domains within a single, homogeneous molecule. This work enables a new dimension of control over specificity, orientation, and stoichiometry of protein domains within atomically precise nanostructures.

PubMed: 34713526
DOI: 10.1002/chem.202103059

Experimental method

X-RAY DIFFRACTION (2 Å)