This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
2dm6
From Proteopedia
| |||||||
| , resolution 2.000Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , and | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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. 2006 Sep;140(3):457-66. Epub 2006 Aug 17. PMID:16916844
Page seeded by OCA on Thu Mar 20 16:28:49 2008
Categories: Cavia porcellus | Single protein | Ago, H. | Hori, T. | Ishijima, J. | Miyano, M. | RSGI, RIKEN Structural Genomics/Proteomics Initiative. | Shimizu, T. | Yokomizo, T. | IMN | NAP | TAM | Nad(p)-binding rossmann-fold domain | Riken structural genomics/proteomics initiative | Rsgi | Structural genomic
