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[[Image:1lo0.jpg|left|200px]]<br /><applet load="1lo0" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1lo0, resolution 2.00&Aring;" />
'''Catalytic Retro-Diels-Alderase Transition State Analogue Complex'''<br />


==Overview==
==Catalytic Retro-Diels-Alderase Transition State Analogue Complex==
The nitroxyl synthase catalytic antibodies 10F11, 9D9, and 27C5 catalyze, the release of nitroxyl from a bicyclic pro-drug by accelerating a, retro-Diels-Alder reaction. The Fabs (antigen-binding fragments) of these, three catalytic antibodies were cloned and sequenced. Fab 9D9 was, crystallized in the apo-form and in complex with one transition state, analogue of the reaction. Crystal structures of Fab 10F11 in complex with, ligands mimicking substrate, transition state, and product have been, determined at resolutions ranging from 1.8 to 2.3 A. Antibodies 9D9 and, 10F11 show increased shape complementarity (as quantified by the program, sc) to the hapten and to a modeled transition state as compared with, substrate and product. The shape complementarity is mediated to a large, extent by an aromatic residue (tyrosine or tryptophan) at the bottom of, the hydrophobic active pocket, which undergoes pi-stacking interactions, with the aromatic rings of the ligands. Another factor contributing to the, different reactivity of the regioisomers probably arises because of, hydrogen-bonding interactions between the nitroxyl bridge and the backbone, amide of PheH101 and possibly a conserved water molecule.
<StructureSection load='1lo0' size='340' side='right'caption='[[1lo0]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1lo0]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LO0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LO0 FirstGlance]. <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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BC1:3-{[(9-CYANO-9,10-DIHYDRO-10-METHYLACRIDIN-9-YL)CARBONYL]AMINO}PROPANOIC+ACID'>BC1</scene></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=1lo0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lo0 OCA], [https://pdbe.org/1lo0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lo0 RCSB], [https://www.ebi.ac.uk/pdbsum/1lo0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lo0 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A2NHM3_MOUSE A2NHM3_MOUSE]
== 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/lo/1lo0_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=1lo0 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The nitroxyl synthase catalytic antibodies 10F11, 9D9, and 27C5 catalyze the release of nitroxyl from a bicyclic pro-drug by accelerating a retro-Diels-Alder reaction. The Fabs (antigen-binding fragments) of these three catalytic antibodies were cloned and sequenced. Fab 9D9 was crystallized in the apo-form and in complex with one transition state analogue of the reaction. Crystal structures of Fab 10F11 in complex with ligands mimicking substrate, transition state, and product have been determined at resolutions ranging from 1.8 to 2.3 A. Antibodies 9D9 and 10F11 show increased shape complementarity (as quantified by the program sc) to the hapten and to a modeled transition state as compared with substrate and product. The shape complementarity is mediated to a large extent by an aromatic residue (tyrosine or tryptophan) at the bottom of the hydrophobic active pocket, which undergoes pi-stacking interactions with the aromatic rings of the ligands. Another factor contributing to the different reactivity of the regioisomers probably arises because of hydrogen-bonding interactions between the nitroxyl bridge and the backbone amide of PheH101 and possibly a conserved water molecule.


==About this Structure==
A structural basis for the activity of retro-Diels-Alder catalytic antibodies: evidence for a catalytic aromatic residue.,Hugot M, Bensel N, Vogel M, Reymond MT, Stadler B, Reymond JL, Baumann U Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9674-8. Epub 2002 Jul 1. PMID:12093912<ref>PMID:12093912</ref>
1LO0 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=BC1:'>BC1</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LO0 OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
A structural basis for the activity of retro-Diels-Alder catalytic antibodies: evidence for a catalytic aromatic residue., Hugot M, Bensel N, Vogel M, Reymond MT, Stadler B, Reymond JL, Baumann U, Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9674-8. Epub 2002 Jul 1. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12093912 12093912]
</div>
<div class="pdbe-citations 1lo0" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Protein complex]]
[[Category: Baumann U]]
[[Category: Baumann, U.]]
[[Category: Hugot M]]
[[Category: Hugot, M.]]
[[Category: Reymond JL]]
[[Category: Reymond, J.L.]]
[[Category: BC1]]
[[Category: catalytic antibody]]
[[Category: fab fragment]]
 
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