Download MendeleyStructural basis for the specificity of the nitric-oxide synthase inhibitors W1400 and Nomega-propyl-L-Arg for the inducible and neuronal isoforms.
Fedorov, R., Hartmann, E., Ghosh, D.K., Schlichting, I.(2003) J Biol Chem 278: 45818-45825
- PubMed: 12954642
- DOI: https://doi.org/10.1074/jbc.M306030200
- Primary Citation of Related Structures:
1QW4, 1QW5, 1QW6, 1QWC - PubMed Abstract:
The high level of amino acid conservation and structural similarity in the immediate vicinity of the substrate binding sites of the oxygenase domains of the nitric-oxide synthase (NOS) isoforms (eNOSoxy, iNOSoxy, and 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 inhibitors W1400 and Nomega-propyl-l-arginine provide a rationale for their isoform specificity. It involves differences outside the immediate active site as well as a conformational flexibility in the active site that allows the adoption of distinct conformations in response to interactions with the inhibitors. This flexibility is determined by isoform-specific residues outside the active site.
Organizational Affiliation:
Max Planck Institut für Molekulare Physiologie, Abteilung Biophysikalische Chemie, Otto Hahn Strasse 11, 44227 Dortmund, Germany.
