1gw6: Difference between revisions
No edit summary |
No edit summary |
||
Line 1: | Line 1: | ||
==STRUCTURE OF LEUKOTRIENE A4 HYDROLASE D375N MUTANT== | ==STRUCTURE OF LEUKOTRIENE A4 HYDROLASE D375N MUTANT== | ||
<StructureSection load='1gw6' size='340' side='right' caption='[[1gw6]], [[Resolution|resolution]] 2.20Å' scene=''> | <StructureSection load='1gw6' size='340' side='right'caption='[[1gw6]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1gw6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GW6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1GW6 FirstGlance]. <br> | <table><tr><td colspan='2'>[[1gw6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GW6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1GW6 FirstGlance]. <br> | ||
Line 30: | Line 30: | ||
</div> | </div> | ||
<div class="pdbe-citations 1gw6" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 1gw6" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Leukotriene A4 Hydrolase|Leukotriene A4 Hydrolase]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
Line 35: | Line 38: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Large Structures]] | |||
[[Category: Haeggstrom, J Z]] | [[Category: Haeggstrom, J Z]] | ||
[[Category: Rudberg, P C]] | [[Category: Rudberg, P C]] |
Revision as of 12:05, 23 October 2019
STRUCTURE OF LEUKOTRIENE A4 HYDROLASE D375N MUTANTSTRUCTURE OF LEUKOTRIENE A4 HYDROLASE D375N MUTANT
Structural highlights
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 PubMedLeukotriene A4 (LTA4, 5S-trans-5,6-oxido-7,9-trans-11,14-cis-eicosatetraenoic acid) hydrolase (LTA4H)/aminopeptidase is a bifunctional zinc metalloenzyme that catalyzes the final and rate-limiting step in the biosynthesis of leukotriene B4 (LTB4, 5S,12R-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid), a classical chemoattractant and immune modulating lipid mediator. Two chemical features are key to the bioactivity of LTB4, namely, the chirality of the 12R-hydroxyl group and the cis-trans-trans geometry of the conjugated triene structure. From the crystal structure of LTA4H, a hydrophilic patch composed of Gln-134, Tyr-267, and Asp-375 was identified in a narrow and otherwise hydrophobic pocket, believed to bind LTA4. In addition, Asp-375 belongs to peptide K21, a previously characterized 21-residue active site-peptide to which LTA4 binds during suicide inactivation. In the present report we used site-directed mutagenesis and x-ray crystallography to show that Asp-375, but none of the other candidate residues, is specifically required for the epoxide hydrolase activity of LTA4H. Thus, mutation of Asp-375 leads to a selective loss of the enzyme's ability to generate LTB4 whereas the aminopeptidase activity is preserved. We propose that Asp-375, possibly assisted by Gln-134, acts as a critical determinant for the stereoselective introduction of the 12R-hydroxyl group and thus the biological activity of LTB4. Leukotriene A4 hydrolase: selective abrogation of leukotriene B4 formation by mutation of aspartic acid 375.,Rudberg PC, Tholander F, Thunnissen MM, Samuelsson B, Haeggstrom JZ Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4215-20. Epub 2002 Mar 26. PMID:11917124[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
|