1p6i
From Proteopedia
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| , resolution 1.90Å | |||||||
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| Ligands: | , , , , | ||||||
| Gene: | NOS1 OR BNOS (Rattus norvegicus) | ||||||
| Activity: | Nitric-oxide synthase, with EC number 1.14.13.39 | ||||||
| Related: | 1P6H, 1P6J, 1P6K, 1P6L, 1P6M, 1P6N
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Rat neuronal NOS heme domain with (4S)-N-(4-amino-5-[aminoethyl]aminopentyl)-N'-nitroguanidine bound
Overview
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
1P6I 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 Sun Mar 30 22:55:35 2008
