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| - | [[Image:1eqg.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1eqg| PDB=1eqg | SCENE= }} | | {{STRUCTURE_1eqg| PDB=1eqg | SCENE= }} |
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| - | '''THE 2.6 ANGSTROM MODEL OF OVINE COX-1 COMPLEXED WITH IBUPROFEN'''
| + | ===THE 2.6 ANGSTROM MODEL OF OVINE COX-1 COMPLEXED WITH IBUPROFEN=== |
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| - | ==Overview==
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| - | Nonsteroidal antiinflammatory drugs (NSAIDs) block prostanoid biosynthesis by inhibiting prostaglandin H(2) synthase (EC 1.14.99.1). NSAIDs are either rapidly reversible competitive inhibitors or slow tight-binding inhibitors of this enzyme. These different modes of inhibition correlate with clinically important differences in isoform selectivity. Hypotheses have been advanced to explain the different inhibition kinetics, but no structural data have been available to test them. We present here crystal structures of prostaglandin H(2) synthase-1 in complex with the inhibitors ibuprofen, methyl flurbiprofen, flurbiprofen, and alclofenac at resolutions ranging from 2.6 to 2.75 A. These structures allow direct comparison of enzyme complexes with reversible competitive inhibitors (ibuprofen and methyl flurbiprofen) and slow tight-binding inhibitors (alclofenac and flurbiprofen). The four inhibitors bind to the same site and adopt similar conformations. In all four complexes, the enzyme structure is essentially unchanged, exhibiting only minimal differences in the inhibitor binding site. These results argue strongly against hypotheses that explain the difference between slow tight-binding and fast reversible competitive inhibition by invoking global conformational differences or different inhibitor binding sites. Instead, they suggest that the different apparent modes of NSAID binding may result from differences in the speed and efficiency with which inhibitors can perturb the hydrogen bonding network around Arg-120 and Tyr-355.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_11318639}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 11318639 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_11318639}} |
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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 Fri May 2 15:24:36 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 01:41:05 2008'' |
Revision as of 22:41, 30 June 2008
Template:STRUCTURE 1eqg
THE 2.6 ANGSTROM MODEL OF OVINE COX-1 COMPLEXED WITH IBUPROFEN
Template:ABSTRACT PUBMED 11318639
About this Structure
1EQG is a Single protein structure of sequence from Ovis aries. Full crystallographic information is available from OCA.
Reference
Structural analysis of NSAID binding by prostaglandin H2 synthase: time-dependent and time-independent inhibitors elicit identical enzyme conformations., Selinsky BS, Gupta K, Sharkey CT, Loll PJ, Biochemistry. 2001 May 1;40(17):5172-80. PMID:11318639
Page seeded by OCA on Tue Jul 1 01:41:05 2008
