1t41

Crystal structure of human aldose reductase complexed with NADP and IDD552

spinqualitylabelsall models 1t41, resolution 1.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1t41 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ID5, NAP Related: 1t40 Activity: Aldehyde reductase, with EC number 1.1.1.21 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ALDR_HUMAN] Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The X-ray crystal structure of human aldose reductase (ALR2) in complex with the inhibitor IDD552 was determined using crystals obtained from two crystallization conditions with different pH values (pH 5 and 8). In both structures the charged carboxylic head of the inhibitor binds to the active site, making hydrogen-bond interactions with His110 and Tyr48 and electrostatic interactions with NADP+. There is an important difference between the two structures: the observation of a double conformation of the carboxylic acid moiety of the inhibitor at pH 8, with one water molecule interacting with the main configuration. This is the first time that a water molecule has been observed deep inside the ALR2 active site. Furthermore, in the configuration with the lower occupancy factor the difference electron-density map shows a clear peak (2.5sigma) for the H atom in the hydrogen bond between the inhibitor's carboxylic acid and the Tyr48 side-chain O atom. The position of this peak implies that this H atom is shared between both O atoms, indicating possible direct proton transfer from this residue to the inhibitor. This fact agrees with the model of the catalytic mechanism, in which the proton is donated by the Tyr48 hydroxyl to the substrate. These observations are useful both in drug design and in understanding the ALR2 mechanism. The crystallographic structure of the aldose reductase-IDD552 complex shows direct proton donation from tyrosine 48.,Ruiz F, Hazemann I, Mitschler A, Joachimiak A, Schneider T, Karplus M, Podjarny A Acta Crystallogr D Biol Crystallogr. 2004 Aug;60(Pt 8):1347-54. Epub 2004, Jul 21. PMID:15272156 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aldose reductase 3D structures

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