3b3m: Difference between revisions

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{{Seed}}
[[Image:3b3m.jpg|left|200px]]


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==Structure of neuronal NOS heme domain in complex with a inhibitor (+-)-3-{cis-4'-[(6"-aminopyridin-2"-yl)methyl]pyrrolidin-3'-ylamino}propan-1-ol==
The line below this paragraph, containing "STRUCTURE_3b3m", creates the "Structure Box" on the page.
<StructureSection load='3b3m' size='340' side='right'caption='[[3b3m]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
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== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[3b3m]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3B3M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3B3M FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=H4B:5,6,7,8-TETRAHYDROBIOPTERIN'>H4B</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=JI1:3-({(3S,4S)-4-[(6-AMINOPYRIDIN-2-YL)METHYL]PYRROLIDIN-3-YL}AMINO)PROPAN-1-OL'>JI1</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
{{STRUCTURE_3b3m|  PDB=3b3m  |  SCENE=  }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3b3m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3b3m OCA], [https://pdbe.org/3b3m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3b3m RCSB], [https://www.ebi.ac.uk/pdbsum/3b3m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3b3m ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NOS1_RAT 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.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b3/3b3m_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3b3m ConSurf].
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<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Fragment hopping, a new fragment-based approach for de novo inhibitor design focusing on ligand diversity and isozyme selectivity, is described. The core of this approach is the derivation of the minimal pharmacophoric element for each pharmacophore. Sites for both ligand binding and isozyme selectivity are considered in deriving the minimal pharmacophoric elements. Five general-purpose libraries are established: the basic fragment library, the bioisostere library, the rules for metabolic stability, the toxicophore library, and the side chain library. These libraries are employed to generate focused fragment libraries to match the minimal pharmacophoric elements for each pharmacophore and then to link the fragment to the desired molecule. This method was successfully applied to neuronal nitric oxide synthase (nNOS), which is implicated in stroke and neurodegenerative diseases. Starting with the nitroarginine-containing dipeptide inhibitors we developed previously, a small organic molecule with a totally different chemical structure was designed, which showed nanomolar nNOS inhibitory potency and more than 1000-fold nNOS selectivity. The crystallographic analysis confirms that the small organic molecule with a constrained conformation can exactly mimic the mode of action of the dipeptide nNOS inhibitors. Therefore, a new peptidomimetic strategy, referred to as fragment hopping, which creates small organic molecules that mimic the biological function of peptides by a pharmacophore-driven strategy for fragment-based de novo design, has been established as a new type of fragment-based inhibitor design. As an open system, the newly established approach efficiently incorporates the concept of early "ADME/Tox" considerations and provides a basic platform for medicinal chemistry-driven efforts.


===Structure of neuronal NOS heme domain in complex with a inhibitor (+-)-3-{cis-4'-[(6"-aminopyridin-2"-yl)methyl]pyrrolidin-3'-ylamino}propan-1-ol===
Minimal pharmacophoric elements and fragment hopping, an approach directed at molecular diversity and isozyme selectivity. Design of selective neuronal nitric oxide synthase inhibitors.,Ji H, Stanton BZ, Igarashi J, Li H, Martasek P, Roman LJ, Poulos TL, Silverman RB J Am Chem Soc. 2008 Mar 26;130(12):3900-14. Epub 2008 Mar 6. PMID:18321097<ref>PMID:18321097</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3b3m" style="background-color:#fffaf0;"></div>


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==See Also==
The line below this paragraph, {{ABSTRACT_PUBMED_18321097}}, adds the Publication Abstract to the page
*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]
(as it appears on PubMed at http://www.pubmed.gov), where 18321097 is the PubMed ID number.
== References ==
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<references/>
{{ABSTRACT_PUBMED_18321097}}
__TOC__
 
</StructureSection>
==About this Structure==
[[Category: Large Structures]]
3B3M is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3B3M OCA].
 
==Reference==
Minimal pharmacophoric elements and fragment hopping, an approach directed at molecular diversity and isozyme selectivity. Design of selective neuronal nitric oxide synthase inhibitors., Ji H, Stanton BZ, Igarashi J, Li H, Martasek P, Roman LJ, Poulos TL, Silverman RB, J Am Chem Soc. 2008 Mar 26;130(12):3900-14. Epub 2008 Mar 6. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18321097 18321097]
[[Category: Nitric-oxide synthase]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
[[Category: Single protein]]
[[Category: Igarashi J]]
[[Category: Igarashi, J.]]
[[Category: Li H]]
[[Category: Li, H.]]
[[Category: Poulos TL]]
[[Category: Poulos, T L.]]
[[Category: Alternative splicing]]
[[Category: Calmodulin-binding]]
[[Category: Cell projection]]
[[Category: Fad]]
[[Category: Fmn]]
[[Category: Heme enzyme]]
[[Category: Inhibitor]]
[[Category: Iron]]
[[Category: Membrane]]
[[Category: Metal-binding]]
[[Category: Nadp]]
[[Category: Nitric oxide synthase]]
[[Category: Oxidoreductase]]
 
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Retrieved from "https://proteopedia.org/3b3m"