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Electrostatic Control of Isoform Selective Inhibitor Binding in Nitric Oxide Synthase.
- Source :
-
Biochemistry [Biochemistry] 2016 Jul 05; Vol. 55 (26), pp. 3702-7. Date of Electronic Publication: 2016 Jun 16. - Publication Year :
- 2016
-
Abstract
- Development of potent and isoform selective nitric oxide synthase (NOS) inhibitors is challenging because of the structural similarity in the heme active sites. One amino acid difference between NOS isoforms, Asp597 in rat neuronal NOS (nNOS) versus Asn368 in bovine endothelial NOS (eNOS), has been identified as the structural basis for why some dipeptide amide inhibitors bind more tightly to nNOS than to eNOS. We now have found that the same amino acid variation is responsible for substantially different binding modes and affinity for a new class of aminopyridine-based inhibitors.
- Subjects :
- Animals
Aspartic Acid chemistry
Aspartic Acid genetics
Cattle
Computational Biology
Isoenzymes
Models, Molecular
Mutation genetics
Nitric Oxide metabolism
Nitric Oxide Synthase Type I chemistry
Nitric Oxide Synthase Type I genetics
Nitric Oxide Synthase Type III chemistry
Nitric Oxide Synthase Type III genetics
Protein Binding
Protein Conformation
Rats
Static Electricity
X-Ray Diffraction
Aminopyridines metabolism
Aspartic Acid metabolism
Enzyme Inhibitors metabolism
Nitric Oxide Synthase Type I metabolism
Nitric Oxide Synthase Type III metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1520-4995
- Volume :
- 55
- Issue :
- 26
- Database :
- MEDLINE
- Journal :
- Biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 27250740
- Full Text :
- https://doi.org/10.1021/acs.biochem.6b00261