1v3t

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{{STRUCTURE_1v3t| PDB=1v3t | SCENE= }}
{{STRUCTURE_1v3t| PDB=1v3t | SCENE= }}
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'''Crystal structure of leukotriene B4 12-hydroxydehydrogenase/15-oxo-prostaglandin 13-reductase'''
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===Crystal structure of leukotriene B4 12-hydroxydehydrogenase/15-oxo-prostaglandin 13-reductase===
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==Overview==
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The bifunctional leukotriene B(4) 12-hydroxydehydrogenase/15-oxo-prostaglandin 13-reductase (LTB(4) 12-HD/PGR) is an essential enzyme for eicosanoid inactivation. It is involved in the metabolism of the E and F series of 15-oxo-prostaglandins (15-oxo-PGs), leukotriene B(4) (LTB(4)), and 15-oxo-lipoxin A(4) (15-oxo-LXA(4)). Some nonsteroidal anti-inflammatory drugs (NSAIDs), which primarily act as cyclooxygenase inhibitors also inhibit LTB(4) 12-HD/PGR activity. Here we report the crystal structure of the LTB(4) 12-HD/PGR, the binary complex structure with NADP(+), and the ternary complex structure with NADP(+) and 15-oxo-PGE(2). In the ternary complex, both in the crystalline form and in solution, the enolate anion intermediate accumulates as a brown chromophore. PGE(2) contains two chains, but only the omega-chain of 15-oxo-PGE(2) was defined in the electron density map in the ternary complex structure. The omega-chain was identified at the hydrophobic pore on the dimer interface. The structure showed that the 15-oxo group forms hydrogen bonds with the 2'-hydroxyl group of nicotine amide ribose of NADP(+) and a bound water molecule to stabilize the enolate intermediate during the reductase reaction. The electron-deficient C13 atom of the conjugated enolate may be directly attacked by a hydride from the NADPH nicotine amide in a stereospecific manner. The moderate recognition of 15-oxo-PGE(2) is consistent with a broad substrate specificity of LTB(4) 12-HD/PGR. The structure also implies that a Src homology domain 3 may interact with the left-handed proline-rich helix at the dimer interface and regulate LTB(4) 12-HD/PGR activity by disruption of the substrate binding pore to accommodate the omega-chain.
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{{ABSTRACT_PUBMED_15007077}}
==About this Structure==
==About this Structure==
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[[Category: Rsgi]]
[[Category: Rsgi]]
[[Category: Structural genomic]]
[[Category: Structural genomic]]
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Revision as of 05:29, 28 July 2008

Template:STRUCTURE 1v3t

Crystal structure of leukotriene B4 12-hydroxydehydrogenase/15-oxo-prostaglandin 13-reductase

Template:ABSTRACT PUBMED 15007077

About this Structure

1V3T is a Single protein structure of sequence from Cavia porcellus. Full crystallographic information is available from OCA.

Reference

Structural basis of leukotriene B4 12-hydroxydehydrogenase/15-Oxo-prostaglandin 13-reductase catalytic mechanism and a possible Src homology 3 domain binding loop., Hori T, Yokomizo T, Ago H, Sugahara M, Ueno G, Yamamoto M, Kumasaka T, Shimizu T, Miyano M, J Biol Chem. 2004 May 21;279(21):22615-23. Epub 2004 Mar 8. PMID:15007077

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