1rs9

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{{STRUCTURE_1rs9| PDB=1rs9 | SCENE= }}
{{STRUCTURE_1rs9| PDB=1rs9 | SCENE= }}
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'''Bovine endothelial NOS heme domain with D-phenylalanine-D-nitroarginine amide bound'''
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===Bovine endothelial NOS heme domain with D-phenylalanine-D-nitroarginine amide bound===
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==Overview==
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In a continuing effort to unravel the structural basis for isoform-selective inhibition of nitric oxide synthase (NOS) by various inhibitors, we have determined the crystal structures of the nNOS and eNOS heme domain bound with two D-nitroarginine-containing dipeptide inhibitors, D-Lys-D-Arg(NO)2-NH(2) and D-Phe-D-Arg(NO)2-NH(2). These two dipeptide inhibitors exhibit similar binding modes in the two constitutive NOS isozymes, which is consistent with the similar binding affinities for the two isoforms as determined by K(i) measurements. The D-nitroarginine-containing dipeptide inhibitors are not distinguished by the amino acid difference between nNOS and eNOS (Asp 597 and Asn 368, respectively) which is key in controlling isoform selection for nNOS over eNOS observed for the L-nitroarginine-containing dipeptide inhibitors reported previously [Flinspach, M., et al. (2004) Nat. Struct. Mol. Biol. 11, 54-59]. The lack of a free alpha-amino group on the D-nitroarginine moiety makes the dipeptide inhibitor steer away from the amino acid binding pocket near the active site. This allows the inhibitor to extend into the solvent-accessible channel farther away from the active site, which enables the inhibitors to explore new isoform-specific enzyme-inhibitor interactions. This might be the structural basis for why these D-nitroarginine-containing inhibitors are selective for nNOS (or eNOS) over iNOS.
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(as it appears on PubMed at http://www.pubmed.gov), where 15122883 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15122883}}
==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 Tue Jul 29 08:44:05 2008''

Revision as of 05:44, 29 July 2008

Image:1rs9.png

Template:STRUCTURE 1rs9

Bovine endothelial NOS heme domain with D-phenylalanine-D-nitroarginine amide bound

Template:ABSTRACT PUBMED 15122883

About this Structure

1RS9 is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.

Reference

Structures of the neuronal and endothelial nitric oxide synthase heme domain with D-nitroarginine-containing dipeptide inhibitors bound., Flinspach M, Li H, Jamal J, Yang W, Huang H, Silverman RB, Poulos TL, Biochemistry. 2004 May 11;43(18):5181-7. PMID:15122883

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