1vaf
From Proteopedia
(New page: 200px<br /><applet load="1vaf" size="450" color="white" frame="true" align="right" spinBox="true" caption="1vaf, resolution 2.9Å" /> '''Inducible nitric oxid...) |
Revision as of 13:33, 21 February 2008
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Inducible nitric oxide synthase oxygenase domain complexed with the inhibitor AR-R17477
Overview
The high level of amino acid conservation and structural similarity of the substrate-binding sites of the oxygenase domains of the nitric oxide synthase (NOS) isoforms (eNOSoxy, iNOSoxy, nNOSoxy) make the interpretation of the structural basis of inhibitor isoform specificity a challenge, and provide few clues for the design of new selective compounds. Crystal structures of iNOSoxy and nNOSoxy complexed with the neuronal NOS-specific inhibitor AR-R17447 suggest that specificity is provided by the interaction of the chlorophenyl group with an isoform-unique substrate access channel residue (L337 in rat neuronal NOS, N115 in mouse inducible NOS). This is confirmed by biochemical analysis of site-directed mutants. Inhibitors combining guanidinium-like structural motifs with long chains specifically targeting this residue are good candidates for rational isoform-specific drug design. Based on this finding, modifications of AR-R17447 to improve the specificity for the human isoforms are suggested.
About this Structure
1VAF is a Single protein structure of sequence from Mus musculus with , , and as ligands. Active as Nitric-oxide synthase, with EC number 1.14.13.39 Full crystallographic information is available from OCA.
Reference
Structures of nitric oxide synthase isoforms complexed with the inhibitor AR-R17477 suggest a rational basis for specificity and inhibitor design., Fedorov R, Vasan R, Ghosh DK, Schlichting I, Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):5892-7. Epub 2004 Apr 7. PMID:15071192
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