3CV7
Crystal structure of porcine aldehyde reductase ternary complex
Summary for 3CV7
Entry DOI | 10.2210/pdb3cv7/pdb |
Related | 2AO0 |
Descriptor | Alcohol dehydrogenase, SULFATE ION, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (5 entities in total) |
Functional Keywords | tim barrel, aldo-keto reductase, ternary complex, acetylation, nadp, oxidoreductase |
Biological source | Sus scrofa (pig) |
Total number of polymer chains | 1 |
Total formula weight | 37961.62 |
Authors | Carbone, V.,El-Kabbani, O. (deposition date: 2008-04-18, release date: 2008-10-28, Last modification date: 2023-11-01) |
Primary citation | Carbone, V.,Chung, R.,Endo, S.,Hara, A.,El-Kabbani, O. Structure of aldehyde reductase in ternary complex with coenzyme and the potent 20alpha-hydroxysteroid dehydrogenase inhibitor 3,5-dichlorosalicylic acid: Implications for inhibitor binding and selectivity Arch.Biochem.Biophys., 479:82-87, 2008 Cited by PubMed Abstract: The structure of aldehyde reductase (ALR1) in ternary complex with the coenzyme NADPH and 3,5-dichlorosalicylic acid (DCL), a potent inhibitor of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1), was determined at a resolution of 2.41A. The inhibitor formed a network of hydrogen bonds with the active site residues Trp22, Tyr50, His113, Trp114 and Arg312. Molecular modelling calculations together with inhibitory activity measurements indicated that DCL was a less potent inhibitor of ALR1 (256-fold) when compared to AKR1C1. In AKR1C1, the inhibitor formed a 10-fold stronger binding interaction with the catalytic residue (Tyr55), non-conserved hydrogen bonding interaction with His222, and additional van der Waals contacts with the non-conserved C-terminal residues Leu306, Leu308 and Phe311 that contribute to the inhibitor's selectivity advantage for AKR1C1 over ALR1. PubMed: 18782556DOI: 10.1016/j.abb.2008.08.014 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.412 Å) |
Structure validation
Download full validation report