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| | {{STRUCTURE_1pgf| PDB=1pgf | SCENE= }} | | {{STRUCTURE_1pgf| PDB=1pgf | SCENE= }} |
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| - | '''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=== |
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| - | ==Overview==
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| - | 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. | + | The line below this paragraph, {{ABSTRACT_PUBMED_8652509}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 8652509 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_8652509}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Oxidoreductase]] | | [[Category: Oxidoreductase]] |
| | [[Category: Peroxidase]] | | [[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 Tue Jul 29 14:30:33 2008'' |
Revision as of 11:30, 29 July 2008
Template:STRUCTURE 1pgf
PROSTAGLANDIN H2 SYNTHASE-1 COMPLEXED WITH 1-(4-IODOBENZOYL)-5-METHOXY-2-METHYLINDOLE-3-ACETIC ACID (IODOINDOMETHACIN), CIS MODEL
Template:ABSTRACT PUBMED 8652509
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 Tue Jul 29 14:30:33 2008
