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| Content Provider | Journal of Biological Chemistry (JBC) |
|---|---|
| Author | Perry, Jason M. Zhao, Yunde Marletta, Michael A. |
| Abstract | Cu2+ and Zn2+inhibit all of the NADPH-dependent reactions catalyzed by neuronal nitric-oxide synthase (nNOS) including ferricytochromec reduction, NADPH oxidation, and citrulline formation. Cu2+ and Zn2+ also inhibit ferricytochromec reduction by the independent reductase domain. Zn2+ affects all activities of the full-length nNOS and the reductase domain to the same extent (estimated IC50 values from 9 to 31 μm), suggesting Zn2+ occupation of a single site in the reductase domain. Citrulline formation and NADPH oxidation by the full-length nNOS and ferricytochromec reduction by the reductase domain are affected similarly by Cu2+, with estimated IC50 values ranging from 6 to 33 μm. However, Cu2+ inhibits ferricytochrome c reduction by the full-length nNOS 2 orders of magnitude more potently, with an estimated IC50value of 0.12 μm. These data suggest the possibility that Cu2+ may interact with nNOS at two sites, one composed exclusively of the reductase domain (which is perhaps also involved in Zn2+-mediated inhibition), and another that includes components of both domains. Occupation of the second (higher affinity) site could then promote the selective inhibition of ferricytochromec reduction in full-length nNOS. Neither the inhibition by Cu2+ nor that by Zn2+ is dependent on calmodulin. |
| Related Links | http://www.jbc.org/content/275/19/14070.abstract |
| Ending Page | 14076 |
| Starting Page | 14070 |
| Page Count | 7 |
| File Format | HTM / HTML PDF |
| ISSN | 00219258 |
| Journal | Journal of Biological Chemistry (JBC) |
| Issue Number | 19 |
| Volume Number | 275 |
| DOI | 10.1074/jbc.275.19.14070 |
| e-ISSN | 1083351X |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 2000-05-12 |
| Access Restriction | Open |
| Subject Keyword | Nitric oxide (NO) Nitric-oxide synthase (NOS) (6R)-5,6,7,8,-tetrahydro-l-biopterin (H4B) Cytochrome P450 reductase (CPR) Neuronal nitric-oxide synthase (nNOS) Calmodulin (CaM) Dithiothreitol (DTT) ENZYME CATALYSIS AND REGULATION |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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