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 language | English (US) |
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Pages (from-to) | 133-139 |
Number of pages | 7 |
Journal | Journal of Inorganic Biochemistry |
Volume | 81 |
Issue number | 3 |
DOIs | |
State | Published - Aug 31 2000 |
Externally published | Yes |
Keywords
- Heme-thiolate enzyme
- Inhibitor design
- Isothiourea
- Nitric oxide synthase
ASJC Scopus subject areas
- Biochemistry
- Inorganic Chemistry