2dm6
From Proteopedia
(New page: 200px<br /><applet load="2dm6" size="450" color="white" frame="true" align="right" spinBox="true" caption="2dm6, resolution 2.000Å" /> '''Crystal structure o...) |
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| - | [[Image:2dm6.gif|left|200px]]<br /><applet load="2dm6" size=" | + | [[Image:2dm6.gif|left|200px]]<br /><applet load="2dm6" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2dm6, resolution 2.000Å" /> | caption="2dm6, resolution 2.000Å" /> | ||
'''Crystal structure of anti-configuration of indomethacin and leukotriene B4 12-hydroxydehydrogenase/15-oxo-prostaglandin 13-reductase complex'''<br /> | '''Crystal structure of anti-configuration of indomethacin and leukotriene B4 12-hydroxydehydrogenase/15-oxo-prostaglandin 13-reductase complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The crystal structure of the ternary complex of leukotriene B4 | + | 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== | ==About this Structure== | ||
| - | 2DM6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Cavia_porcellus Cavia porcellus] with NAP, IMN and TAM as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2DM6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Cavia_porcellus Cavia porcellus] with <scene name='pdbligand=NAP:'>NAP</scene>, <scene name='pdbligand=IMN:'>IMN</scene> and <scene name='pdbligand=TAM:'>TAM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DM6 OCA]. |
==Reference== | ==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 | + | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16916844 16916844] |
[[Category: Cavia porcellus]] | [[Category: Cavia porcellus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| Line 17: | Line 17: | ||
[[Category: Ishijima, J.]] | [[Category: Ishijima, J.]] | ||
[[Category: Miyano, M.]] | [[Category: Miyano, M.]] | ||
| - | [[Category: RSGI, RIKEN | + | [[Category: RSGI, RIKEN Structural Genomics/Proteomics Initiative.]] |
[[Category: Shimizu, T.]] | [[Category: Shimizu, T.]] | ||
[[Category: Yokomizo, T.]] | [[Category: Yokomizo, T.]] | ||
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[[Category: structural genomics]] | [[Category: structural genomics]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:00:14 2008'' |
Revision as of 15:00, 21 February 2008
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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 , and 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. 2006 Sep;140(3):457-66. Epub 2006 Aug 17. PMID:16916844
Page seeded by OCA on Thu Feb 21 17:00:14 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 domains | Riken structural genomics/proteomics initiative | Rsgi | Structural genomics
