1pgf
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1pgf.gif|left|200px]] | [[Image:1pgf.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1pgf", 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_1pgf| PDB=1pgf | SCENE= }} |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''PROSTAGLANDIN H2 SYNTHASE-1 COMPLEXED WITH 1-(4-IODOBENZOYL)-5-METHOXY-2-METHYLINDOLE-3-ACETIC ACID (IODOINDOMETHACIN), CIS MODEL''' | '''PROSTAGLANDIN H2 SYNTHASE-1 COMPLEXED WITH 1-(4-IODOBENZOYL)-5-METHOXY-2-METHYLINDOLE-3-ACETIC ACID (IODOINDOMETHACIN), CIS MODEL''' | ||
| Line 29: | Line 26: | ||
[[Category: Loll, P J.]] | [[Category: Loll, P J.]] | ||
[[Category: Picot, D.]] | [[Category: Picot, D.]] | ||
| - | [[Category: | + | [[Category: Dioxygenase]] |
| - | [[Category: | + | [[Category: Oxidoreductase]] |
| - | [[Category: | + | [[Category: Peroxidase]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:03:38 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 02:03, 3 May 2008
PROSTAGLANDIN H2 SYNTHASE-1 COMPLEXED WITH 1-(4-IODOBENZOYL)-5-METHOXY-2-METHYLINDOLE-3-ACETIC ACID (IODOINDOMETHACIN), CIS MODEL
Overview
The cyclooxygenase activity of the membrane protein prostaglandin H2 synthase isoform 1 (PGHS-1) is the target of the nonsteroidal antiinflammatory drugs (NSAIDs). The X-ray crystal structures of PGHS-1 in complex with the NSAIDs flurbiprofen and bromoaspirin have been determined previously [Picot, D., et al. (1994) Nature 367, 243-249; Loll, P. J., et al. (1995) Nat. Struct. Biol. 2, 637-643]. We report here the preparation and characterization of novel potent iodinated analogs of the NSAIDs indomethacin and suprofen, as well as the refined X-ray crystal structures of their complexes with PGHS-1. The PGHS-iodosuprofen complex structure has been refined at 3.5 A to an R-value of 0.189 and shows the suprofen analog to share a common mode of binding with flurbiprofen. The PGHS-iodoindomethacin complex structure has been refined at 4.5 A to an R-value of 0.254. The low resolution of the iodoindomethacin complex structure precludes detailed modeling of drug-enzyme interactions, but the electron-dense iodine atom of the inhibitor has been unambiguously located, allowing for the placement and approximate orientation of the inhibitor in the enzyme's active site. We have modeled two equally likely binding modes for iodoindomethacin, corresponding to the two principal conformers of the inhibitor. Like flurbiprofen, iodosuprofen and iodoindomethacin bind at the end of the long channel which leads into the enzyme active site. Binding at this site presumably blocks access of substrate to Tyr-385, a residue essential for catalysis. No evidence is seen for significant protein conformational differences between the iodoindomethacin and iodosuprofen of flurbiprofen complex structures.
About this Structure
1PGF is a Single protein structure of sequence from Ovis aries. Full crystallographic information is available from OCA.
Reference
Synthesis and use of iodinated nonsteroidal antiinflammatory drug analogs as crystallographic probes of the prostaglandin H2 synthase cyclooxygenase active site., Loll PJ, Picot D, Ekabo O, Garavito RM, Biochemistry. 1996 Jun 11;35(23):7330-40. PMID:8652509 Page seeded by OCA on Sat May 3 05:03:38 2008
