1D1V
BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH S-ETHYL-N-PHENYL-ISOTHIOUREA (H4B BOUND)
Summary for 1D1V
| Entry DOI | 10.2210/pdb1d1v/pdb |
| Related | 1D0C 1D0O 1D1V 1D1W 1D1X 1D1Y 1NSE |
| Descriptor | BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME, ACETATE ION, ZINC ION, ... (9 entities in total) |
| Functional Keywords | alpha-beta fold, oxidoreductase |
| Biological source | Bos taurus (cattle) |
| Cellular location | Cell membrane: P29473 |
| Total number of polymer chains | 2 |
| Total formula weight | 102257.99 |
| Authors | Raman, C.S.,Li, H.,Martasek, P.,Southan, G.J.,Masters, B.S.S.,Poulos, T.L. (deposition date: 1999-09-21, release date: 2001-07-25, Last modification date: 2024-02-07) |
| Primary citation | Raman, C.S.,Li, H.,Martasek, P.,Babu, B.R.,Griffith, O.W.,Masters, B.S.,Poulos, T.L. Implications for isoform-selective inhibitor design derived from the binding mode of bulky isothioureas to the heme domain of endothelial nitric-oxide synthase. J.Biol.Chem., 276:26486-26491, 2001 Cited by PubMed Abstract: Nitric oxide produced by nitric-oxide synthase (NOS) is not only involved in a wide range of physiological functions but also in a variety of pathological conditions. Isoform-selective NOS inhibitors are highly desirable to regulate the NO production of one isoform beneficial to normal physiological functions from the uncontrolled NO production of another isoform that accompanies certain pathological states. Crystal structures of the heme domain of the three NOS isoforms have revealed a very high degree of similarity in the immediate vicinity of the heme active site illustrating the challenge of isoform-selective inhibitor design. Isothioureas are potent NOS inhibitors, and the structures of the endothelial NOS heme domain complexed with isothioureas bearing small S-alkyl substituents have been determined (Li, H., Raman, C.S., Martásek, P., Král, V., Masters, B.S.S., and Poulos, T.L. (2000) J. Inorg. Biochem. 81, 133--139). In the present communication, the binding mode of larger bisisothioureas complexed to the endothelial NOS heme domain has been determined. These structures afford a structural rationale for the known inhibitory activities. In addition, these structures provide clues on how to exploit the longer inhibitor substituents that extend out of the active site pocket for isoform-selective inhibitor design. PubMed: 11331290DOI: 10.1074/jbc.M102255200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.93 Å) |
Structure validation
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