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4kch

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Revision as of 23:05, 5 August 2016

Structure of neuronal nitric oxide synthase heme domain in complex with N,N'-([1,1'-biphenyl]-3,3'-diyl)bis(thiophene-2-carboximidamide)

Structural highlights

4kch is a 2 chain structure with sequence from Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
Related:	4kci, 4kcj, 4kck, 4kcl, 4kcm, 4kcn, 4kco, 4kcp, 4kcq, 4kcr, 4kcs
Gene:	Nos1, Bnos (Buffalo rat)
Activity:	Nitric-oxide synthase (NADPH dependent), with EC number 1.14.13.39
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[NOS1_RAT] Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR. Inhibitory transmitter for non-adrenergic and non-cholinergic nerves in the colorectum.

Publication Abstract from PubMed

Selective inhibitors of neuronal nitric oxide synthase (nNOS) are regarded as valuable and powerful agents with therapeutic potential for the treatment of chronic neurodegenerative pathologies and human melanoma. Here, we describe a novel hybrid strategy that combines the pharmacokinetically promising thiophene-2-carboximidamide fragment and structural features of our previously reported potent and selective aminopyridine inhibitors. Two inhibitors, 13 and 14, show low nanomolar inhibitory potency (Ki = 5 nM for nNOS) and good isoform selectivities (nNOS over eNOS [440- and 540-fold, respectively] and over iNOS [260- and 340-fold, respectively]). The crystal structures of these nNOS-inhibitor complexes reveal a new hot spot that explains the selectivity of 14 and why converting the secondary to tertiary amine leads to enhanced selectivity. More importantly, these compounds are the first highly potent and selective nNOS inhibitory agents that exhibit excellent in vitro efficacy in melanoma cell lines.

Potent and Selective Double-Headed Thiophene-2-carboximidamide Inhibitors of Neuronal Nitric Oxide Synthase for the Treatment of Melanoma.,Huang H, Li H, Yang S, Chreifi G, Martasek P, Roman LJ, Meyskens FL, Poulos TL, Silverman RB J Med Chem. 2014 Jan 30. PMID:24447275^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Huang H, Li H, Yang S, Chreifi G, Martasek P, Roman LJ, Meyskens FL, Poulos TL, Silverman RB. Potent and Selective Double-Headed Thiophene-2-carboximidamide Inhibitors of Neuronal Nitric Oxide Synthase for the Treatment of Melanoma. J Med Chem. 2014 Jan 30. PMID:24447275 doi:http://dx.doi.org/10.1021/jm401252e

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4kch"

Categories: Buffalo rat | Li, H | Poulos, T L | Nitric oxide synthase | Oxidoreductase-oxidoreductase inhibitor complex

@@ Line 1: / Line 1: @@
 ==Structure of neuronal nitric oxide synthase heme domain in complex with N,N'-([1,1'-biphenyl]-3,3'-diyl)bis(thiophene-2-carboximidamide)==
 <StructureSection load='4kch' size='340' side='right' caption='[[4kch]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Nos1, Bnos ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Nitric-oxide_synthase_(NADPH_dependent) Nitric-oxide synthase (NADPH dependent)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.39 1.14.13.39] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4kch FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kch OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4kch RCSB], [http://www.ebi.ac.uk/pdbsum/4kch PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4kch FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kch OCA], [http://pdbe.org/4kch PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kch RCSB], [http://www.ebi.ac.uk/pdbsum/4kch PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kch ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4kch" style="background-color:#fffaf0;"></div>
 ==See Also==

4kch

From Proteopedia

Revision as of 23:05, 5 August 2016

Structure of neuronal nitric oxide synthase heme domain in complex with N,N'-([1,1'-biphenyl]-3,3'-diyl)bis(thiophene-2-carboximidamide)

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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