5G0N

Structure of rat neuronal nitric oxide synthase D597N mutant heme domain in complex with N1-(5-(2-(6-AMINO-4-METHYLPYRIDIN-2-YL)ETHYL) PYRIDIN-3-YL)-N1,N2-DIMETHYLETHANE-1,2-DIAMINE

Summary for 5G0N

• Entry DOI: 10.2210/pdb5g0n/pdb
• Related: 5G0O 5G0P
• Descriptor: NITRIC OXIDE SYNTHASE, BRAIN, PROTOPORPHYRIN IX CONTAINING FE, 5,6,7,8-TETRAHYDROBIOPTERIN, ... (7 entities in total)
• Functional Keywords: oxidoreductase, nitric oxide synthase, inhibitor complex
• Biological source: RATTUS NORVEGICUS (NORWAY RAT)
• Cellular location: Cell membrane, sarcolemma ; Peripheral membrane protein : P29476
• Total number of polymer chains: 2
• Total formula weight: 100120.88

Authors

Li, H.,Poulos, T.L. (deposition date: 2016-03-21, release date: 2016-06-15, Last modification date: 2024-05-08)

Primary citation

Li, H.,Wang, H.,Kang, S.,Silverman, R.B.,Poulos, T.L.
Electrostatic Control of Isoform Selective Inhibitor Binding in Nitric Oxide Synthase.
Biochemistry, 55:3702-, 2016

PubMed 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.

PubMed: 27250740
DOI: 10.1021/ACS.BIOCHEM.6B00261

Experimental method

X-RAY DIFFRACTION (1.936 Å)