1gw6: Difference between revisions
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[[Image:1gw6.jpg|left|200px]] | [[Image:1gw6.jpg|left|200px]] | ||
'''STRUCTURE OF LEUKOTRIENE A4 HYDROLASE D375N MUTANT''' | {{Structure | ||
|PDB= 1gw6 |SIZE=350|CAPTION= <scene name='initialview01'>1gw6</scene>, resolution 2.20Å | |||
|SITE= <scene name='pdbsite=BES:Zn+Binding+Site+For+Chain+A'>BES</scene> | |||
|LIGAND= <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=YB:YTTERBIUM+(III)+ION'>YB</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=BES:2-(3-AMINO-2-HYDROXY-4-PHENYL-BUTYRYLAMINO)-4-METHYL-PENTANOIC+ACID'>BES</scene> and <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Leukotriene-A(4)_hydrolase Leukotriene-A(4) hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.3.2.6 3.3.2.6] | |||
|GENE= | |||
}} | |||
'''STRUCTURE OF LEUKOTRIENE A4 HYDROLASE D375N MUTANT''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1GW6 is a [ | 1GW6 is a [[Single protein]] structure of 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=1GW6 OCA]. | ||
==Reference== | ==Reference== | ||
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:// | 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: Leukotriene-A(4) hydrolase]] | [[Category: Leukotriene-A(4) hydrolase]] | ||
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[[Category: alpha-beta protein]] | [[Category: alpha-beta protein]] | ||
[[Category: hydrolase]] | [[Category: hydrolase]] | ||
[[Category: mutagenesis | [[Category: mutagenesis study]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:28:50 2008'' | ||
Revision as of 12:28, 20 March 2008
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| , resolution 2.20Å | |||||||
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| Sites: | |||||||
| Ligands: | , , , and | ||||||
| Activity: | Leukotriene-A(4) hydrolase, with EC number 3.3.2.6 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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
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