1h19

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|PDB= 1h19 |SIZE=350|CAPTION= <scene name='initialview01'>1h19</scene>, resolution 2.1&Aring;
|PDB= 1h19 |SIZE=350|CAPTION= <scene name='initialview01'>1h19</scene>, resolution 2.1&Aring;
|SITE= <scene name='pdbsite=ZN1:Imd+Binding+Site+For+Chain+A'>ZN1</scene>
|SITE= <scene name='pdbsite=ZN1:Imd+Binding+Site+For+Chain+A'>ZN1</scene>
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|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>
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|LIGAND= <scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=YB:YTTERBIUM+(III)+ION'>YB</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
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|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]
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|ACTIVITY= <span class='plainlinks'>[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] </span>
|GENE=
|GENE=
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|DOMAIN=
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1h19 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h19 OCA], [http://www.ebi.ac.uk/pdbsum/1h19 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1h19 RCSB]</span>
}}
}}
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[[Category: Tholander, F.]]
[[Category: Tholander, F.]]
[[Category: Thunnissen, M M.G M.]]
[[Category: Thunnissen, M M.G M.]]
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[[Category: ACY]]
 
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[[Category: IMD]]
 
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[[Category: YB]]
 
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[[Category: ZN]]
 
[[Category: alpha-beta protein]]
[[Category: alpha-beta protein]]
[[Category: hydrolase]]
[[Category: hydrolase]]
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[[Category: metalloprotease]]
[[Category: metalloprotease]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:30:49 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:55:44 2008''

Revision as of 17:55, 30 March 2008


PDB ID 1h19

Drag the structure with the mouse to rotate
, resolution 2.1Å
Sites:
Ligands: , , ,
Activity: Leukotriene-A(4) hydrolase, with EC number 3.3.2.6
Resources: FirstGlance, OCA, PDBsum, RCSB
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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