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1p6j

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{{STRUCTURE_1p6j| PDB=1p6j | SCENE= }}
{{STRUCTURE_1p6j| PDB=1p6j | SCENE= }}
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'''Rat neuronal NOS heme domain with L-N(omega)-nitroarginine-(4R)-amino-L-proline amide bound'''
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===Rat neuronal NOS heme domain with L-N(omega)-nitroarginine-(4R)-amino-L-proline amide bound===
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==Overview==
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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 &gt;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.
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{{ABSTRACT_PUBMED_14718923}}
==About this Structure==
==About this Structure==
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[[Category: Nitric oxide synthase]]
[[Category: Nitric oxide synthase]]
[[Category: Oxidoreductase]]
[[Category: Oxidoreductase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 04:44:49 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 06:40:02 2008''

Revision as of 03:40, 28 July 2008

Image:1p6j.png

Template:STRUCTURE 1p6j

Rat neuronal NOS heme domain with L-N(omega)-nitroarginine-(4R)-amino-L-proline amide bound

Template:ABSTRACT PUBMED 14718923

About this Structure

1P6J is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.

Reference

Structural basis for dipeptide amide isoform-selective inhibition of neuronal nitric oxide synthase., Flinspach ML, Li H, Jamal J, Yang W, Huang H, Hah JM, Gomez-Vidal JA, Litzinger EA, Silverman RB, Poulos TL, Nat Struct Mol Biol. 2004 Jan;11(1):54-9. Epub 2003 Dec 29. PMID:14718923

Page seeded by OCA on Mon Jul 28 06:40:02 2008

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