2dm6

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spinqualitylabelsall models 2dm6, resolution 2.000Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of anti-configuration of indomethacin and leukotriene B4 12-hydroxydehydrogenase/15-oxo-prostaglandin 13-reductase complex

Overview

The crystal structure of the ternary complex of leukotriene B4, 12-hydroxydehydrogenase/15-oxo-prostaglandin (15-oxo-PG) 13-reductase, (LTB4 12HD/PGR), an essential enzyme for eicosanoid inactivation pathways, with indomethacin and NADP+ has been solved. An indomethacin molecule, bound in the anti-configuration at one of the two active site clefts of, the homo-dimer interface in the LTB4 12HD/PGR and was confirmed by a, binding calorimetry. The chlorobenzene ring is buried in the hydrophobic, pore used as a binding site by the omega-chain of 15-oxo-PGE2. The, carboxyl group interacts with the guanidino group of Arg56 and the, phenolic hydroxyl group of Tyr262. Indomethacin shows a broad spectrum of, efficacy against lipid-mediator related proteins including, cyclooxygenase-2, phospholipase A2, PGF synthase and PGE synthase-2 but in, the syn-configuration as well as LTB4 12HD/PGR in the anti-configuration., Indomethacin does not necessarily mimic the binding mode of the, lipid-mediator substrates in the active sites of these complex structures., Thus, the broad spectrum of indomethacin efficacy can be attributed to its, ability to adopt a range of different stable conformations. This allows, the indomethacin to adapt to the distinct binding site features of each, protein whilst maintaining favorable interactions between the carboxyl, group and a counter charged functional group.

About this Structure

2DM6 is a Single protein structure of sequence from Cavia porcellus with NAP, IMN and TAM as ligands. Full crystallographic information is available from OCA.

Reference

Crystal structure of anti-configuration of indomethacin and leukotriene B4 12-hydroxydehydrogenase/15-oxo-prostaglandin 13-reductase complex reveals the structural basis of broad spectrum indomethacin efficacy., Hori T, Ishijima J, Yokomizo T, Ago H, Shimizu T, Miyano M, J Biochem (Tokyo). 2006 Sep;140(3):457-66. Epub 2006 Aug 17. PMID:16916844

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