1h19
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1h19.jpg|left|200px]] | [[Image:1h19.jpg|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1h19", 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_1h19| PDB=1h19 | SCENE= }} |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''STRUCTURE OF [E271Q] LEUKOTRIENE A4 HYDROLASE''' | '''STRUCTURE OF [E271Q] LEUKOTRIENE A4 HYDROLASE''' | ||
| Line 24: | Line 21: | ||
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] | 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: Single protein]] | [[Category: Single protein]] | ||
[[Category: Haeggstrom, J Z.]] | [[Category: Haeggstrom, J Z.]] | ||
| Line 30: | Line 26: | ||
[[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: Leukotriene biosynthesis]] |
| - | [[Category: | + | [[Category: Metalloprotease]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 18:17:24 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 15:17, 2 May 2008
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 Page seeded by OCA on Fri May 2 18:17:24 2008
