1p6j: Difference between revisions
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New page: left|200px<br /><applet load="1p6j" size="450" color="white" frame="true" align="right" spinBox="true" caption="1p6j, resolution 2.00Å" /> '''Rat neuronal NOS hem... |
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[[Image:1p6j.jpg|left|200px]]<br /><applet load="1p6j" size=" | [[Image:1p6j.jpg|left|200px]]<br /><applet load="1p6j" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1p6j, resolution 2.00Å" /> | caption="1p6j, resolution 2.00Å" /> | ||
'''Rat neuronal NOS heme domain with L-N(omega)-nitroarginine-(4R)-amino-L-proline amide bound'''<br /> | '''Rat neuronal NOS heme domain with L-N(omega)-nitroarginine-(4R)-amino-L-proline amide bound'''<br /> | ||
==Overview== | ==Overview== | ||
Three nitric oxide synthase (NOS) isoforms, eNOS, nNOS and iNOS, generate | 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-N(omega)-nitroarginine-containing dipeptide inhibitors. | ||
==About this Structure== | ==About this Structure== | ||
1P6J is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with ACT, ZN, HEM, H4B and DP9 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Nitric-oxide_synthase Nitric-oxide synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.39 1.14.13.39] Full crystallographic information is available from [http:// | 1P6J is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=ACT:'>ACT</scene>, <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=HEM:'>HEM</scene>, <scene name='pdbligand=H4B:'>H4B</scene> and <scene name='pdbligand=DP9:'>DP9</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Nitric-oxide_synthase Nitric-oxide synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.39 1.14.13.39] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P6J OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Flinspach, M | [[Category: Flinspach, M L.]] | ||
[[Category: Gomez-Vidal, J | [[Category: Gomez-Vidal, J A.]] | ||
[[Category: Hah, J | [[Category: Hah, J M.]] | ||
[[Category: Huang, H.]] | [[Category: Huang, H.]] | ||
[[Category: Jamal, J.]] | [[Category: Jamal, J.]] | ||
[[Category: Li, H.]] | [[Category: Li, H.]] | ||
[[Category: Litzinger, E | [[Category: Litzinger, E A.]] | ||
[[Category: Poulos, T | [[Category: Poulos, T L.]] | ||
[[Category: Silverman, R | [[Category: Silverman, R B.]] | ||
[[Category: Yang, W.]] | [[Category: Yang, W.]] | ||
[[Category: ACT]] | [[Category: ACT]] | ||
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[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:25:44 2008'' | ||
