4QXI

Crystal structure of human AR complexed with NADP+ and AK198

Summary for 4QXI

• Entry DOI: 10.2210/pdb4qxi/pdb
• Related: 1US0 2IKI
• Descriptor: Aldose reductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, {2-[(4-amino-2-fluorobenzyl)carbamoyl]-5-chlorophenoxy}acetic acid, ... (4 entities in total)
• Functional Keywords: tim barrel, aldose reductase, oxidoreductase, diabetes, halogenated compound, cytosolic
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P15121
• Total number of polymer chains: 1
• Total formula weight: 36994.49

Authors

Cousido-Siah, A.,Mitschler, A.,Ruiz, F.X.,Fanfrlik, J.,Hobza, P.,Podjarny, A.D. (deposition date: 2014-07-21, release date: 2015-07-22, Last modification date: 2023-11-08)

Primary citation

Fanfrlik, J.,Ruiz, F.X.,Kadlcikova, A.,Rezac, J.,Cousido-Siah, A.,Mitschler, A.,Haldar, S.,Lepsik, M.,Kolar, M.H.,Majer, P.,Podjarny, A.D.,Hobza, P.
The Effect of Halogen-to-Hydrogen Bond Substitution on Human Aldose Reductase Inhibition.
Acs Chem.Biol., 10:1637-1642, 2015

PubMed Abstract: The effect of halogen-to-hydrogen bond substitution on the binding energetics and biological activity of a human aldose reductase inhibitor has been studied using X-ray crystallography, IC50 measurements, advanced binding free energy calculations, and simulations. The replacement of Br or I atoms by an amine (NH2) group has not induced changes in the original geometry of the complex, which made it possible to study the isolated features of selected noncovalent interactions in a biomolecular complex.

PubMed: 25919404
DOI: 10.1021/acschembio.5b00151

Experimental method

X-RAY DIFFRACTION (0.867 Å)