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2r59

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Revision as of 15:49, 20 November 2019

Leukotriene A4 hydrolase complexed with inhibitor RB3041

Structural highlights

2r59 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Related:	1hs6, 1h19, 1sqm, 1gw6
Gene:	LTA4H, LTA4 (Homo sapiens)
Activity:	Leukotriene-A(4) hydrolase, with EC number 3.3.2.6
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[LKHA4_HUMAN] Epoxide hydrolase that catalyzes the final step in the biosynthesis of the proinflammatory mediator leukotriene B4. Has also aminopeptidase activity.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

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

M1 aminopeptidases comprise a large family of biologically important zinc enzymes. We show that peptide turnover by the M1 prototype, leukotriene A4 hydrolase/aminopeptidase, involves a shift in substrate position associated with exchange of zinc coordinating groups, while maintaining the overall coordination geometry. The transition state is stabilized by residues conserved among M1 members and in the final reaction step, Glu-296 of the canonical zinc binding HEXXH motif shuffles a proton from the hydrolytic water to the leaving group. Tripeptide substrates bind along the conserved GXMEN motif, precisely occupying the distance between Glu-271 and Arg-563, whereas the Arg specificity is governed by a narrow S1 pocket capped with Asp-375. Our data provide detailed insights to the active site chemistry of M1 aminopeptidases and will aid in the development of novel enzyme inhibitors.

Structure-based dissection of the active site chemistry of leukotriene A4 hydrolase: implications for M1 aminopeptidases and inhibitor design.,Tholander F, Muroya A, Roques BP, Fournie-Zaluski MC, Thunnissen MM, Haeggstrom JZ Chem Biol. 2008 Sep 22;15(9):920-9. PMID:18804029^[8]

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

References

↑ Odlander B, Claesson HE, Bergman T, Radmark O, Jornvall H, Haeggstrom JZ. Leukotriene A4 hydrolase in the human B-lymphocytic cell line Raji: indications of catalytically divergent forms of the enzyme. Arch Biochem Biophys. 1991 May 15;287(1):167-74. PMID:1897988
↑ Toh H, Minami M, Shimizu T. Molecular evolution and zinc ion binding motif of leukotriene A4 hydrolase. Biochem Biophys Res Commun. 1990 Aug 31;171(1):216-21. PMID:1975494
↑ Haeggstrom JZ, Wetterholm A, Shapiro R, Vallee BL, Samuelsson B. Leukotriene A4 hydrolase: a zinc metalloenzyme. Biochem Biophys Res Commun. 1990 Nov 15;172(3):965-70. PMID:2244921
↑ Thunnissen MM, Andersson B, Samuelsson B, Wong CH, Haeggstrom JZ. Crystal structures of leukotriene A4 hydrolase in complex with captopril and two competitive tight-binding inhibitors. FASEB J. 2002 Oct;16(12):1648-50. Epub 2002 Aug 7. PMID:12207002 doi:10.1096/fj.01-1017fje
↑ Rudberg PC, Tholander F, Thunnissen MM, Samuelsson B, Haeggstrom JZ. Leukotriene A4 hydrolase: selective abrogation of leukotriene B4 formation by mutation of aspartic acid 375. Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4215-20. Epub 2002 Mar 26. PMID:11917124 doi:10.1073/pnas.072090099
↑ Rudberg PC, Tholander F, Andberg M, Thunnissen MM, Haeggstrom JZ. Leukotriene A4 hydrolase: identification of a common carboxylate recognition site for the epoxide hydrolase and aminopeptidase substrates. J Biol Chem. 2004 Jun 25;279(26):27376-82. Epub 2004 Apr 12. PMID:15078870 doi:10.1074/jbc.M401031200
↑ Tholander F, Muroya A, Roques BP, Fournie-Zaluski MC, Thunnissen MM, Haeggstrom JZ. Structure-based dissection of the active site chemistry of leukotriene A4 hydrolase: implications for M1 aminopeptidases and inhibitor design. Chem Biol. 2008 Sep 22;15(9):920-9. PMID:18804029 doi:10.1016/j.chembiol.2008.07.018
↑ Tholander F, Muroya A, Roques BP, Fournie-Zaluski MC, Thunnissen MM, Haeggstrom JZ. Structure-based dissection of the active site chemistry of leukotriene A4 hydrolase: implications for M1 aminopeptidases and inhibitor design. Chem Biol. 2008 Sep 22;15(9):920-9. PMID:18804029 doi:10.1016/j.chembiol.2008.07.018

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/2r59"

@@ Line 1: / Line 1: @@
 ==Leukotriene A4 hydrolase complexed with inhibitor RB3041==
-<StructureSection load='2r59' size='340' side='right' caption='[[2r59]], [[Resolution|resolution]] 1.89&Aring;' scene=''>
+<StructureSection load='2r59' size='340' side='right'caption='[[2r59]], [[Resolution|resolution]] 1.89&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2r59]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R59 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2R59 FirstGlance]. <br>
@@ Line 39: / Line 39: @@
 </StructureSection>
 [[Category: Homo sapiens]]
+[[Category: Large Structures]]
 [[Category: Fournie-Zaluski, M C]]
 [[Category: Haeggstrom, J Z]]

2r59

From Proteopedia

Revision as of 15:49, 20 November 2019

Leukotriene A4 hydrolase complexed with inhibitor RB3041

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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