3e7g: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
(5 intermediate revisions by the same user not shown)
Line 1: Line 1:
==Structure of human INOSOX with inhibitor AR-C95791==
==Structure of human INOSOX with inhibitor AR-C95791==
<StructureSection load='3e7g' size='340' side='right' caption='[[3e7g]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
<StructureSection load='3e7g' size='340' side='right'caption='[[3e7g]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3e7g]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E7G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3E7G FirstGlance]. <br>
<table><tr><td colspan='2'>[[3e7g]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E7G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3E7G FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AT2:ETHYL+4-[(4-METHYLPYRIDIN-2-YL)AMINO]PIPERIDINE-1-CARBOXYLATE'>AT2</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=ZN:ZINC+ION'>ZN</scene><br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3e65|3e65]], [[3e67|3e67]], [[3e68|3e68]], [[3e6l|3e6l]], [[3e6n|3e6n]], [[3e6o|3e6o]], [[3e6t|3e6t]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AT2:ETHYL+4-[(4-METHYLPYRIDIN-2-YL)AMINO]PIPERIDINE-1-CARBOXYLATE'>AT2</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=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Nitric-oxide_synthase Nitric-oxide synthase], 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'>[https://proteopedia.org/fgij/fg.htm?mol=3e7g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e7g OCA], [https://pdbe.org/3e7g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3e7g RCSB], [https://www.ebi.ac.uk/pdbsum/3e7g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3e7g ProSAT]</span></td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3e7g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e7g OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3e7g RCSB], [http://www.ebi.ac.uk/pdbsum/3e7g PDBsum]</span></td></tr>
</table>
<table>
== Function ==
[https://www.uniprot.org/uniprot/NOS2_HUMAN NOS2_HUMAN] Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such COX2.
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e7/3e7g_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e7/3e7g_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </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/chain_selection.php?pdb_ID=2ata ConSurf].
</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=3e7g ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Nitric oxide synthase (NOS) enzymes synthesize nitric oxide, a signal for vasodilatation and neurotransmission at low concentrations and a defensive cytotoxin at higher concentrations. The high active site conservation among all three NOS isozymes hinders the design of selective NOS inhibitors to treat inflammation, arthritis, stroke, septic shock and cancer. Our crystal structures and mutagenesis results identified an isozyme-specific induced-fit binding mode linking a cascade of conformational changes to a new specificity pocket. Plasticity of an isozyme-specific triad of distant second- and third-shell residues modulates conformational changes of invariant first-shell residues to determine inhibitor selectivity. To design potent and selective NOS inhibitors, we developed the anchored plasticity approach: anchor an inhibitor core in a conserved binding pocket, then extend rigid bulky substituents toward remote specificity pockets, which become accessible upon conformational changes of flexible residues. This approach exemplifies general principles for the design of selective enzyme inhibitors that overcome strong active site conservation.
Anchored plasticity opens doors for selective inhibitor design in nitric oxide synthase.,Garcin ED, Arvai AS, Rosenfeld RJ, Kroeger MD, Crane BR, Andersson G, Andrews G, Hamley PJ, Mallinder PR, Nicholls DJ, St-Gallay SA, Tinker AC, Gensmantel NP, Mete A, Cheshire DR, Connolly S, Stuehr DJ, Aberg A, Wallace AV, Tainer JA, Getzoff ED Nat Chem Biol. 2008 Nov;4(11):700-7. Epub 2008 Oct 12. PMID:18849972<ref>PMID:18849972</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>


==See Also==
==See Also==
*[[Nitric Oxide Synthase|Nitric Oxide Synthase]]
*[[Nitric Oxide Synthase 3D structures|Nitric Oxide Synthase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Nitric-oxide synthase]]
[[Category: Large Structures]]
[[Category: Aberg, A.]]
[[Category: Aberg A]]
[[Category: Andersson, G.]]
[[Category: Andersson G]]
[[Category: Andrews, G.]]
[[Category: Andrews G]]
[[Category: Arvai, A S.]]
[[Category: Arvai AS]]
[[Category: Cheshire, D R.]]
[[Category: Cheshire DR]]
[[Category: Connolly, S.]]
[[Category: Connolly S]]
[[Category: Crane, B R.]]
[[Category: Crane BR]]
[[Category: Garcin, E D.]]
[[Category: Garcin ED]]
[[Category: Gensmantel, N P.]]
[[Category: Gensmantel NP]]
[[Category: Getzoff, E D.]]
[[Category: Getzoff ED]]
[[Category: Hamley, P J.]]
[[Category: Hamley PJ]]
[[Category: Kroeger, M D.]]
[[Category: Kroeger MD]]
[[Category: Mallinder, P R.]]
[[Category: Mallinder PR]]
[[Category: Mete, A.]]
[[Category: Mete A]]
[[Category: Nicholls, D J.]]
[[Category: Nicholls DJ]]
[[Category: Rosenfeld, R J.]]
[[Category: Rosenfeld RJ]]
[[Category: St-Gallay, S A.]]
[[Category: St-Gallay SA]]
[[Category: Stueh, D J.]]
[[Category: Stueh DJ]]
[[Category: Tainer, J A.]]
[[Category: Tainer JA]]
[[Category: Tinker, A C.]]
[[Category: Tinker AC]]
[[Category: Wallace, A V.]]
[[Category: Wallace AV]]
[[Category: Calmodulin-binding]]
[[Category: Fad]]
[[Category: Fmn]]
[[Category: Heme]]
[[Category: Iron]]
[[Category: Metal-binding]]
[[Category: Nadp]]
[[Category: Nitric oxide]]
[[Category: No]]
[[Category: Oxidoreductase]]
[[Category: Phosphoprotein]]
[[Category: Tetrahydrobiopterin]]

Latest revision as of 12:45, 21 February 2024

Structure of human INOSOX with inhibitor AR-C95791Structure of human INOSOX with inhibitor AR-C95791

Structural highlights

3e7g is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.2Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NOS2_HUMAN Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such COX2.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

3e7g, resolution 2.20Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=3e7g&oldid=4064457"