1u67
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1u67.jpg|left|200px]] | [[Image:1u67.jpg|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1u67", 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_1u67| PDB=1u67 | SCENE= }} |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''Crystal Structure of Arachidonic Acid Bound to a Mutant of Prostagladin H Synthase-1 that Forms Predominantly 11-HPETE.''' | '''Crystal Structure of Arachidonic Acid Bound to a Mutant of Prostagladin H Synthase-1 that Forms Predominantly 11-HPETE.''' | ||
| Line 31: | Line 28: | ||
[[Category: Smith, W L.]] | [[Category: Smith, W L.]] | ||
[[Category: 11-hete]] | [[Category: 11-hete]] | ||
| - | [[Category: | + | [[Category: Arachidonic acid]] |
| - | [[Category: | + | [[Category: Cox-1]] |
| - | [[Category: | + | [[Category: Cox-2]] |
| - | [[Category: | + | [[Category: Cyclooxgenase]] |
| - | [[Category: | + | [[Category: Eicosanoid]] |
| - | [[Category: | + | [[Category: Heme]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 10:48:21 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 07:48, 3 May 2008
Crystal Structure of Arachidonic Acid Bound to a Mutant of Prostagladin H Synthase-1 that Forms Predominantly 11-HPETE.
Overview
Kinetic studies and analysis of the products formed by native and mutant forms of ovine prostaglandin endoperoxide H synthase-1 (oPGHS-1) have suggested that arachidonic acid (AA) can exist in the cyclooxygenase active site of the enzyme in three different, catalytically competent conformations that lead to prostaglandin G2 (PGG2), 11R-hydroperoxyeicosatetraenoic acid (HPETE), and 15R,S-HPETE, respectively. We have identified an oPGHS-1 mutant (V349A/W387F) that forms predominantly 11R-HPETE. Thus, the preferred catalytically competent arrangement of AA in the cyclooxygenase site of this double mutant must be one that leads to 11-HPETE. The crystal structure of Co3+-protoporphyrin IX V349A/W387F oPGHS-1 in a complex with AA was determined to 3.1 A. Significant differences are observed in the positions of atoms C-3, C-4, C-5, C-6, C-10, C-11, and C-12 of bound AA between native and V349A/W387F oPGHS-1; in comparison, the positions of the side chains of cyclooxygenase active site residues are unchanged. The structure of the double mutant presented here provides structural insight as to how Val349 and Trp387 help position C-9 and C-11 of AA so that the incipient 11-peroxyl radical intermediate is able to add to C-9 to form the 9,11 endoperoxide group of PGG2. In the V349A/W387F oPGHS-1.AA complex the locations of C-9 and C-11 of AA with respect to one another make it difficult to form the endoperoxide group from the 11-hydroperoxyl radical. Therefore, the reaction apparently aborts yielding 11R-HPETE instead of PGG2. In addition, the observed differences in the positions of carbon atoms of AA bound to this mutant provides indirect support for the concept that the conformer of AA shown previously to be bound within the cyclooxygenase active site of native oPGHS-1 is the one that leads to PGG2.
About this Structure
1U67 is a Single protein structure of sequence from Ovis aries. Full crystallographic information is available from OCA.
Reference
Crystal structure of arachidonic acid bound to a mutant of prostaglandin endoperoxide H synthase-1 that forms predominantly 11-hydroperoxyeicosatetraenoic acid., Harman CA, Rieke CJ, Garavito RM, Smith WL, J Biol Chem. 2004 Oct 8;279(41):42929-35. Epub 2004 Jul 30. PMID:15292194 Page seeded by OCA on Sat May 3 10:48:21 2008
