1h19: Difference between revisions
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[[Image:1h19.jpg|left|200px]] | [[Image:1h19.jpg|left|200px]] | ||
'''STRUCTURE OF [E271Q] LEUKOTRIENE A4 HYDROLASE''' | {{Structure | ||
|PDB= 1h19 |SIZE=350|CAPTION= <scene name='initialview01'>1h19</scene>, resolution 2.1Å | |||
|SITE= <scene name='pdbsite=ZN1:Imd+Binding+Site+For+Chain+A'>ZN1</scene> | |||
|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=YB:YTTERBIUM+(III)+ION'>YB</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene> and <scene name='pdbligand=ACY:ACETIC ACID'>ACY</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 [E271Q] LEUKOTRIENE A4 HYDROLASE''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1H19 is a [ | 1H19 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=1H19 OCA]. | ||
==Reference== | ==Reference== | ||
Leukotriene A4 hydrolase/aminopeptidase. Glutamate 271 is a catalytic residue with specific roles in two distinct enzyme mechanisms., Rudberg PC, Tholander F, Thunnissen MM, Haeggstrom JZ, J Biol Chem. 2002 Jan 11;277(2):1398-404. Epub 2001 Oct 23. PMID:[http:// | Leukotriene A4 hydrolase/aminopeptidase. Glutamate 271 is a catalytic residue with specific roles in two distinct enzyme mechanisms., Rudberg PC, Tholander F, Thunnissen MM, Haeggstrom JZ, J Biol Chem. 2002 Jan 11;277(2):1398-404. Epub 2001 Oct 23. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11675384 11675384] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Leukotriene-A(4) hydrolase]] | [[Category: Leukotriene-A(4) hydrolase]] | ||
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[[Category: metalloprotease]] | [[Category: metalloprotease]] | ||
''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 11:30:49 2008'' | ||
Revision as of 09:30, 20 March 2008
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| 1h19, resolution 2.1Å | |||||||||||||
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| Sites: | ZN1 | ||||||||||||
| Ligands: | ZN, YB, IMD and ACY | ||||||||||||
| Activity: | Leukotriene-A(4) hydrolase, with EC number 3.3.2.6 | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
STRUCTURE OF [E271Q] LEUKOTRIENE A4 HYDROLASE
Overview
Leukotriene A(4) hydrolase/aminopeptidase is a bifunctional zinc metalloenzyme that converts the fatty acid epoxide leukotriene A(4) into leukotriene B(4), a potent chemoattractant and immune-modulating lipid mediator. Recently, the structure of leukotriene A(4) hydrolase revealed that Glu-271, which belongs to a conserved GXMEN motif in the M1 family of zinc peptidases, and Gln-136 are located at the active site. Here we report that mutagenetic replacements of Glu-271, but not Gln-136, abrogate both catalytic activities of leukotriene A(4) hydrolase. Furthermore, the 2.1 A crystal structure of [E271Q]leukotriene A(4) hydrolase revealed minimal conformational changes that could not explain the loss of enzyme function. We propose that the carboxylate of Glu-271 participates in an acid-induced opening of the epoxide moiety of leukotriene A(4) and formation of a carbocation intermediate. Moreover, Glu-271 appears to act as an N-terminal recognition site and may potentially stabilize the transition-state during turnover of peptides, a property that most likely pertains to all members of the M1 family of zinc aminopeptidases. Hence, Glu-271 is a unique example of an amino acid, which has dual and separate functions in two different catalytic reactions, involving lipid and peptide substrates, respectively.
About this Structure
1H19 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Leukotriene A4 hydrolase/aminopeptidase. Glutamate 271 is a catalytic residue with specific roles in two distinct enzyme mechanisms., Rudberg PC, Tholander F, Thunnissen MM, Haeggstrom JZ, J Biol Chem. 2002 Jan 11;277(2):1398-404. Epub 2001 Oct 23. PMID:11675384
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