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4upm

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Revision as of 08:22, 5 August 2016

Structure of rat neuronal nitric oxide synthase heme domain in complex with N',N'-{[(2R)-3-aminopropane-1,2-diyl]bis(oxymethanediylbenzene-3,1-diyl)}dithiophene-2-carboximidamide

Structural highlights

4upm is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , ,
Related:	4upn, 4upo, 4upp, 4upq, 4upr, 4ups, 4upt
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

To develop potent and selective nNOS inhibitors, a new series of double-headed molecules with chiral linkers that derive from natural amino acid derivatives have been designed and synthesized. The new structures integrate a thiophenecarboximidamide head with two types of chiral linkers, presenting easy synthesis and good inhibitory properties. Inhibitor (S)-9b exhibits a potency of 14.7nM against nNOS and is 1134 and 322-fold more selective for nNOS over eNOS and iNOS, respectively. Crystal structures show that the additional binding between the aminomethyl moiety of 9b and propionate A on the heme and tetrahydrobiopterin (H4B) in nNOS, but not eNOS, contributes to its high selectivity. This work demonstrates the advantage of integrating known structures into structure optimization, and it should be possible to more readily develop compounds that incorporate bioavailability with these advanced features. Moreover, this integrative strategy is a general approach in new drug discovery.

Combination of chiral linkers with thiophenecarboximidamide heads to improve the selectivity of inhibitors of neuronal nitric oxide synthase.,Jing Q, Li H, Roman LJ, Martasek P, Poulos TL, Silverman RB Bioorg Med Chem Lett. 2014 Aug 12. pii: S0960-894X(14)00814-2. doi:, 10.1016/j.bmcl.2014.07.079. PMID:25149509^[1]

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

References

↑ Jing Q, Li H, Roman LJ, Martasek P, Poulos TL, Silverman RB. Combination of chiral linkers with thiophenecarboximidamide heads to improve the selectivity of inhibitors of neuronal nitric oxide synthase. Bioorg Med Chem Lett. 2014 Aug 12. pii: S0960-894X(14)00814-2. doi:, 10.1016/j.bmcl.2014.07.079. PMID:25149509 doi:http://dx.doi.org/10.1016/j.bmcl.2014.07.079

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/4upm"

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

@@ Line 1: / Line 1: @@
 ==Structure of rat neuronal nitric oxide synthase heme domain in complex with N',N'-{[(2R)-3-aminopropane-1,2-diyl]bis(oxymethanediylbenzene-3,1-diyl)}dithiophene-2-carboximidamide==
 <StructureSection load='4upm' size='340' side='right' caption='[[4upm]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4upn|4upn]], [[4upo|4upo]], [[4upp|4upp]], [[4upq|4upq]], [[4upr|4upr]], [[4ups|4ups]], [[4upt|4upt]]</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=4upm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4upm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4upm RCSB], [http://www.ebi.ac.uk/pdbsum/4upm 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=4upm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4upm OCA], [http://pdbe.org/4upm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4upm RCSB], [http://www.ebi.ac.uk/pdbsum/4upm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4upm 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 4upm" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4upm

From Proteopedia

Revision as of 08:22, 5 August 2016

Structure of rat neuronal nitric oxide synthase heme domain in complex with N',N'-{[(2R)-3-aminopropane-1,2-diyl]bis(oxymethanediylbenzene-3,1-diyl)}dithiophene-2-carboximidamide

Structural highlights

Function

Publication Abstract from PubMed

References

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Proteopedia Page Contributors and Editors (what is this?)

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