1gw6: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1gw6.jpg|left|200px]] | [[Image:1gw6.jpg|left|200px]] | ||
<!-- | |||
The line below this paragraph, containing "STRUCTURE_1gw6", creates the "Structure Box" on the page. | |||
You may change the PDB parameter (which sets the PDB file loaded into the applet) | |||
or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |||
or leave the SCENE parameter empty for the default display. | |||
| | --> | ||
| | {{STRUCTURE_1gw6| PDB=1gw6 | SCENE= }} | ||
}} | |||
'''STRUCTURE OF LEUKOTRIENE A4 HYDROLASE D375N MUTANT''' | '''STRUCTURE OF LEUKOTRIENE A4 HYDROLASE D375N MUTANT''' | ||
| Line 24: | Line 21: | ||
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:[http://www.ncbi.nlm.nih.gov/pubmed/11917124 11917124] | 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:[http://www.ncbi.nlm.nih.gov/pubmed/11917124 11917124] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Haeggstrom, J Z.]] | [[Category: Haeggstrom, J Z.]] | ||
| Line 31: | Line 27: | ||
[[Category: Tholander, F.]] | [[Category: Tholander, F.]] | ||
[[Category: Thunnissen, M M.G M.]] | [[Category: Thunnissen, M M.G M.]] | ||
[[Category: | [[Category: Alpha-beta protein]] | ||
[[Category: | [[Category: Hydrolase]] | ||
[[Category: | [[Category: Mutagenesis study]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 18:05:08 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 18:05, 2 May 2008
STRUCTURE OF LEUKOTRIENE A4 HYDROLASE D375N MUTANT
OverviewOverview
Leukotriene 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.
About this StructureAbout this Structure
1GW6 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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 Page seeded by OCA on Fri May 2 18:05:08 2008