1vaf
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(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...)
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Revision as of 02:25, 21 November 2007
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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 ZN, HEM, H4B and ARR 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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