Mapping the active site polarity in structures of endothelial nitric oxide synthase heme domain complexed with isothioureas

Huiying Li, C. S. Raman, Pavel Martásek, Vladimir Král, Bettie Sue S. Masters, Thomas L. Poulos

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Analyzing the active site topology and plasticity of nitric oxide synthase (NOS) and understanding enzyme-drug interactions are crucial for the development of potent, isoform-selective NOS inhibitors. A small hydrophobic pocket in the active site is identified in the bovine eNOS heme domain structures complexed with potent isothiourea inhibitors: seleno analogue of S-ethyl-isothiourea, S-isopropyl-isothiourea, and 2-aminothiazoline, respectively. These structures reveal the importance of nonpolar van der Waals contacts in addition to the well-known hydrogen bonding interactions between inhibitor and enzyme. The scaffold of a potent NOS inhibitor should be capable of donating hydrogen bonds to as well as making nonpolar contacts with amino acids in the NOS active site. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)133-139
Number of pages7
JournalJournal of Inorganic Biochemistry
Volume81
Issue number3
DOIs
StatePublished - Aug 31 2000

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Keywords

  • Heme-thiolate enzyme
  • Inhibitor design
  • Isothiourea
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry

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