Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 하정미 | - |
dc.date.accessioned | 2020-03-02T05:14:24Z | - |
dc.date.available | 2020-03-02T05:14:24Z | - |
dc.date.issued | 2004-01 | - |
dc.identifier.citation | NATURE STRUCTURAL & MOLECULAR BIOLOGY, v. 11, No. 1, Page. 54-59 | en_US |
dc.identifier.issn | 1545-9993 | - |
dc.identifier.issn | 1545-9985 | - |
dc.identifier.uri | https://www.nature.com/articles/nsmb704 | - |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/132007 | - |
dc.description.abstract | Three nitric oxide synthase (NOS) isoforms, eNOS, nNOS and iNOS, generate nitric oxide (NO) crucial to the cardiovascular, nervous and host defense systems, respectively. Development of isoform-selective NOS inhibitors is of considerable therapeutic importance. Crystal structures of nNOS-selective dipeptide inhibitors in complex with both nNOS and eNOS were solved and the inhibitors were found to adopt a curled conformation in nNOS but an extended conformation in eNOS. We hypothesized that a single-residue difference in the active site, Asp597 (nNOS) versus Asn368 (eNOS), is responsible for the favored binding in nNOS. In the D597N nNOS mutant crystal structure, a bound inhibitor switches to the extended conformation and its inhibition of nNOS decreases >200-fold. Therefore, a single-residue difference is responsible for more than two orders of magnitude selectivity in inhibition of nNOS over eNOS by L-Nω-nitroarginine-containing dipeptide inhibitors. | en_US |
dc.description.sponsorship | We thank the beamline staff at SSRL and ALS for their assistance during synchrotron data collection. This research was supported by US National Institutes of Health grants GM57353 (T.L.P) and GM49725 (R.B.S.). J.A.G. acknowledges NATO and the Spanish Ministry of Science and Technology for support. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | NATURE PUBLISHING GROUP | en_US |
dc.title | Structural basis for dipeptide amide isoform-selective inhibition of neuronal nitric oxide synthase | en_US |
dc.type | Article | en_US |
dc.relation.no | 1 | - |
dc.relation.volume | 11 | - |
dc.identifier.doi | 10.1038/nsmb704 | - |
dc.relation.page | 54-59 | - |
dc.relation.journal | NATURE STRUCTURAL & MOLECULAR BIOLOGY | - |
dc.contributor.googleauthor | Flinspach, Mack L | - |
dc.contributor.googleauthor | Li, Huiying | - |
dc.contributor.googleauthor | Jamal, Joumana | - |
dc.contributor.googleauthor | Yang, Weiping | - |
dc.contributor.googleauthor | Huang, Hui | - |
dc.contributor.googleauthor | Hah, Jung-Mi | - |
dc.contributor.googleauthor | Gómez-Vidal, José Antonio | - |
dc.contributor.googleauthor | Litzinger, Elizabeth A | - |
dc.contributor.googleauthor | Silverman, Richard B | - |
dc.contributor.googleauthor | Poulos, Thomas L | - |
dc.relation.code | 2009211943 | - |
dc.sector.campus | E | - |
dc.sector.daehak | COLLEGE OF PHARMACY[E] | - |
dc.sector.department | DEPARTMENT OF PHARMACY | - |
dc.identifier.pid | jhah | - |
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