4QXI

Crystal structure of human AR complexed with NADP+ and AK198

PDB DOI: https://doi.org/10.2210/pdb4QXI/pdb

Classification: OXIDOREDUCTASE
Organism(s): Homo sapiens
Expression System: Escherichia coli BL21(DE3)
Mutation(s): No

Deposited: 2014-07-21 Released: 2015-07-22
Deposition Author(s): Cousido-Siah, A., Mitschler, A., Ruiz, F.X., Fanfrlik, J., Hobza, P., Podjarny, A.D.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 0.87 Å
R-Value Free: 0.145
R-Value Work: 0.134
R-Value Observed: 0.134

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.2 of the entry. See complete history.

Literature

The Effect of Halogen-to-Hydrogen Bond Substitution on Human Aldose Reductase Inhibition.

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.

(2015) ACS Chem Biol 10: 1637-1642

PubMed: 25919404 Search on PubMed
DOI: https://doi.org/10.1021/acschembio.5b00151
Primary Citation of Related Structures:
4QXI

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.

Organizational Affiliation

†Institute of Organic Chemistry and Biochemistry (IOCB) and Gilead Science and IOCB Research Center, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic.

Macromolecule Content

Total Structure Weight: 36.99 kDa
Atom Count: 3,194
Modelled Residue Count: 314
Deposited Residue Count: 316
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Aldose reductase	A	316	Homo sapiens	Mutation(s): 0 Gene Names: AKR1B1, ALDR1 EC: 1.1.1.21
UniProt & NIH Common Fund Data Resources
Find proteins for P15121 (Homo sapiens) Explore P15121 Go to UniProtKB: P15121
PHAROS: P15121 GTEx: ENSG00000085662
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P15121
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
NAP Query on NAP Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A]	B [auth A]	NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE C₂₁ H₂₈ N₇ O₁₇ P₃ XJLXINKUBYWONI-NNYOXOHSSA-N		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]
I98 Query on I98 Download Ideal Coordinates CCD File SDF format, chain C [auth A] MOL2 format, chain C [auth A]	C [auth A]	{2-[(4-amino-2-fluorobenzyl)carbamoyl]-5-chlorophenoxy}acetic acid C₁₆ H₁₄ Cl F N₂ O₄ GFJYPJDGRCZNDI-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]