Electrostatic Control of Isoform Selective Inhibitor Binding in Nitric Oxide Synthase
- 주제(기타) Biochemistry & Molecular Biology
- 등재 SCIE, SCOPUS
- 발행기관 AMER CHEMICAL SOC
- 발행년도 2016
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000162050
- 본문언어 영어
- Published As http://dx.doi.org/10.1021/acs.biochem.6b00261
초록/요약
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.
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