title: The structure of human aldose reductase bound to the inhibitor IDD384.
abstract: The crystallographic structure of the complex between human aldose reductase (AR2) and one of its inhibitors, IDD384, has been solved at 1.7 A resolution from crystals obtained at pH 5.0. This structure shows that the binding of the inhibitor's hydrophilic head to the catalytic residues Tyr48 and His110 differs from that found previously with porcine AR2. The difference is attributed to a change in the protonation state of the inhibitor (pK(a) = 4.52) when soaked with crystals of human (at pH 5.0) or pig lens AR2 (at pH 6.2). This work demonstrates how strongly the detailed binding of the inhibitor's polar head depends on its protonation state.
authors.affiliation: UPR de Biologie Structurale 9004, IGBMC, CNRS/INSERM/ULP, 1 Rue Laurent Fries, BP 163, 67404 Illkirch, France.
authors.forename: V
authors.initials: V
authors.lastname: Calderone
authors.forename: B
authors.initials: B
authors.lastname: Chevrier
authors.forename: M
authors.initials: M
authors.lastname: Van Zandt
authors.forename: V
authors.initials: V
authors.lastname: Lamour
authors.forename: E
authors.initials: E
authors.lastname: Howard
authors.forename: A
authors.initials: A
authors.lastname: Poterszman
authors.forename: P
authors.initials: P
authors.lastname: Barth
authors.forename: A
authors.initials: A
authors.lastname: Mitschler
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.forename: D M
authors.initials: DM
authors.lastname: Dvornik
authors.forename: G
authors.initials: G
authors.lastname: Klebe
authors.forename: O
authors.initials: O
authors.lastname: Kraemer
authors.forename: A R
authors.initials: AR
authors.lastname: Moorman
authors.forename: D
authors.initials: D
authors.lastname: Moras
authors.forename: A
authors.initials: A
authors.lastname: Podjarny
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000737:chemistry*; D000595:Amino Acid Sequence; D000818:Animals; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D004563:Electrochemistry; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013450:Sulfones / Q000737:chemistry* / Q000494:pharmacology; D013552:Swine
chemical_list: D004791:Enzyme Inhibitors; C412449:IDD384; D011994:Recombinant Proteins; D013450:Sulfones; D000449:Aldehyde Reductase