Electrostatic Control of Isoform Selective Inhibitor Binding in Nitric Oxide Synthase

Huiying Li, Heng Yen Wang, Soosung Kang, Richard B. Silverman*, Thomas L. Poulos

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3702-3707
Number of pages6
JournalBiochemistry
Volume55
Issue number26
DOIs
StatePublished - Jul 5 2016

ASJC Scopus subject areas

  • Biochemistry

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