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4ctp

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Revision as of 23:57, 4 August 2016

Structure of rat neuronal nitric oxide synthase heme domain in complex with (S)-6-(2-Amino-2-(3-(2-(6-amino-4-methylpyridin-2-yl) ethyl)phenyl)ethyl)-4-methylpyridin-2-amine

Structural highlights

4ctp is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
Related:	4ctq, 4ctr, 4ctt, 4ctu, 4ctv, 4ctw, 4ctx, 4cty, 4ctz, 4cu0, 4cu1
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

Overproduction of NO by nNOS is implicated in the pathogenesis of diverse neuronal disorders. Since NO signaling is involved in diverse physiological functions, selective inhibition of nNOS over other isoforms is essential to minimize side effects. A series of alpha-amino functionalized aminopyridine derivatives (3 - 8) were designed to probe the structure-activity relationship between ligand, heme propionate, and H4B. Compound 8R was identified as the most potent and selective molecule of this study, exhibiting a Ki of 24 nM for nNOS, with 273-fold and 2822-fold selectivity against iNOS and eNOS, respectively. Although crystal structures of 8R complexed with nNOS and eNOS revealed a similar binding mode, the selectivity stems from the distinct electrostatic environments in two isoforms that result in much lower inhibitor binding free energy in nNOS than in eNOS. These findings provide a basis for further development of simple, but even more selective and potent, nNOS inhibitors.

Nitric Oxide Synthase Inhibitors that Interact with both a Heme Propionate and Tetrahydrobiopterin Show High Isoform Selectivity.,Kang S, Tang W, Li H, Chreifi G, Martasek P, Roman LJ, Poulos TL, Silverman RB J Med Chem. 2014 Apr 23. PMID:24758147^[1]

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

References

↑ Kang S, Tang W, Li H, Chreifi G, Martasek P, Roman LJ, Poulos TL, Silverman RB. Nitric Oxide Synthase Inhibitors that Interact with both a Heme Propionate and Tetrahydrobiopterin Show High Isoform Selectivity. J Med Chem. 2014 Apr 23. PMID:24758147 doi:http://dx.doi.org/10.1021/jm5004182

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

Categories: Li, H | Poulos, T L | Inhibitor complex | Nitric oxide synthase | Oxidoreductase

@@ Line 1: / Line 1: @@
 ==Structure of rat neuronal nitric oxide synthase heme domain in complex with (S)-6-(2-Amino-2-(3-(2-(6-amino-4-methylpyridin-2-yl) ethyl)phenyl)ethyl)-4-methylpyridin-2-amine==
 <StructureSection load='4ctp' size='340' side='right' caption='[[4ctp]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ctq|4ctq]], [[4ctr|4ctr]], [[4ctt|4ctt]], [[4ctu|4ctu]], [[4ctv|4ctv]], [[4ctw|4ctw]], [[4ctx|4ctx]], [[4cty|4cty]], [[4ctz|4ctz]], [[4cu0|4cu0]], [[4cu1|4cu1]]</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=4ctp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ctp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ctp RCSB], [http://www.ebi.ac.uk/pdbsum/4ctp 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=4ctp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ctp OCA], [http://pdbe.org/4ctp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ctp RCSB], [http://www.ebi.ac.uk/pdbsum/4ctp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ctp ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4ctp" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4ctp

From Proteopedia

Revision as of 23:57, 4 August 2016

Structure of rat neuronal nitric oxide synthase heme domain in complex with (S)-6-(2-Amino-2-(3-(2-(6-amino-4-methylpyridin-2-yl) ethyl)phenyl)ethyl)-4-methylpyridin-2-amine

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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