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1v3u

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Revision as of 13:04, 1 January 2020

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

Structural highlights

1v3u is a 2 chain structure with sequence from Cavpo. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1v3t, 1v3v
Activity:	15-oxoprostaglandin 13-oxidase, with EC number 1.3.1.48
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT, TOPSAN

Function

[PTGR1_CAVPO] Functions as 15-oxo-prostaglandin 13-reductase and acts on 15-oxo-PGE1, 15-oxo-PGE2 and 15-oxo-PGE2-alpha. Catalyzes the conversion of leukotriene B4 into its biologically less active metabolite, 12-oxo-leukotriene B4. This is an initial and key step of metabolic inactivation of leukotriene B4.

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 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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hori T, Yokomizo T, Ago H, Sugahara M, Ueno G, Yamamoto M, Kumasaka T, Shimizu T, Miyano M. Structural basis of leukotriene B4 12-hydroxydehydrogenase/15-Oxo-prostaglandin 13-reductase catalytic mechanism and a possible Src homology 3 domain binding loop. J Biol Chem. 2004 May 21;279(21):22615-23. Epub 2004 Mar 8. PMID:15007077 doi:10.1074/jbc.M312655200

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1v3u"

@@ Line 1: / Line 1: @@
 ==Crystal structure of leukotriene B4 12-hydroxydehydrogenase/15-oxo-prostaglandin 13-reductase in apo form==
-<StructureSection load='1v3u' size='340' side='right' caption='[[1v3u]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='1v3u' size='340' side='right'caption='[[1v3u]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1v3u]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Cavpo Cavpo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1V3U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1V3U FirstGlance]. <br>
@@ Line 39: / Line 39: @@
 [[Category: 15-oxoprostaglandin 13-oxidase]]
 [[Category: Cavpo]]
+[[Category: Large Structures]]
 [[Category: Ago, H]]
 [[Category: Hori, T]]

1v3u

From Proteopedia

Revision as of 13:04, 1 January 2020

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

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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