Research output per year
Research output per year
Description
Experimental Technique/Method:X-RAY DIFFRACTION
Resolution:1.5
Classification:OXIDOREDUCTASE
Release Date:2017-02-15
Deposition Date:2016-10-12
Revision Date:2017-11-22
Molecular Weight:37679.97
Macromolecule Type:Protein
Residue Count:316
Atom Site Count:2686
DOI:10.2210/pdb5m2f/pdb
Abstract:
UVI2008, a retinoic acid receptor (RAR) β/γ agonist originated from C3 bromine addition to the parent RAR pan-agonist 4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid (TTNPB), is also a selective inhibitor of aldo-keto reductase family member 1B10 (AKR1B10). Thus, it might become a lead drug for the design of compounds targeting both activities, as an AKR1B10 inhibitor and RAR agonist, which could constitute a novel therapeutic approach against cancer and skin-related diseases. Herein, the X-ray structure of the methylated Lys125Arg/Val301Leu AKR1B10 (i.e. AKME2MU) holoenzyme in complex with UVI2008 was determined at 1.5 Å resolution, providing an explanation for UVI2008 selectivity against AKR1B10 (IC
Resolution:1.5
Classification:OXIDOREDUCTASE
Release Date:2017-02-15
Deposition Date:2016-10-12
Revision Date:2017-11-22
Molecular Weight:37679.97
Macromolecule Type:Protein
Residue Count:316
Atom Site Count:2686
DOI:10.2210/pdb5m2f/pdb
Abstract:
UVI2008, a retinoic acid receptor (RAR) β/γ agonist originated from C3 bromine addition to the parent RAR pan-agonist 4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid (TTNPB), is also a selective inhibitor of aldo-keto reductase family member 1B10 (AKR1B10). Thus, it might become a lead drug for the design of compounds targeting both activities, as an AKR1B10 inhibitor and RAR agonist, which could constitute a novel therapeutic approach against cancer and skin-related diseases. Herein, the X-ray structure of the methylated Lys125Arg/Val301Leu AKR1B10 (i.e. AKME2MU) holoenzyme in complex with UVI2008 was determined at 1.5 Å resolution, providing an explanation for UVI2008 selectivity against AKR1B10 (IC
| Date made available | 15 Feb 2017 |
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Research output
- 1 Article
-
Structural basis for the inhibition of AKR1B10 by the C3 brominated TTNPB derivative UVI2008
Ruiz, F. X., Crespo, I., Álvarez, S., Porté, S., Giménez-Dejoz, J., Cousido-Siah, A., Mitschler, A., de Lera, Á. R., Parés, X., Podjarny, A. & Farrés, J., 1 Oct 2017, In: Chemico-Biological Interactions. 276, p. 174-181Research output: Contribution to journal › Article › Research › peer-review
4 Citations (Scopus)