1a3l

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: 200px<br /> <applet load="1a3l" size="450" color="white" frame="true" align="right" spinBox="true" caption="1a3l, resolution 1.95&Aring;" /> '''CATALYSIS OF A DISF...)
Current revision (06:21, 30 October 2024) (edit) (undo)
 
(18 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1a3l.gif|left|200px]]<br />
 
-
<applet load="1a3l" size="450" color="white" frame="true" align="right" spinBox="true"
 
-
caption="1a3l, resolution 1.95&Aring;" />
 
-
'''CATALYSIS OF A DISFAVORED REACTION: AN ANTIBODY EXO DIELS-ALDERASE-TSA-INHIBITOR COMPLEX AT 1.95 A RESOLUTION'''<br />
 
-
==Overview==
+
==CATALYSIS OF A DISFAVORED REACTION: AN ANTIBODY EXO DIELS-ALDERASE-TSA-INHIBITOR COMPLEX AT 1.95 A RESOLUTION==
-
A highly specific Diels-Alder protein catalyst was made by manipulating, the antibody repertoire of the immune system. The catalytic antibody 13G5, catalyzes a disfavored exo Diels-Alder transformation in a reaction for, which there is no natural enzyme counterpart and that yields a single, regioisomer in high enantiomeric excess. The crystal structure of the, antibody Fab in complex with a ferrocenyl inhibitor containing the, essential haptenic core that elicited 13G5 was determined at 1.95 angstrom, resolution. Three key antibody residues appear to be responsible for the, observed catalysis and product control. Tyrosine-L36 acts as a Lewis acid, activating the dienophile for nucleophilic attack, and asparagine-L91 and, aspartic acid-H50 form hydrogen bonds to the carboxylate side chain that, substitutes for the carbamate diene substrate. This hydrogen-bonding, scheme leads to rate acceleration and also pronounced stereoselectivity., Docking experiments with the four possible ortho transition states of the, reaction explain the specific exo effect and suggest that the (3R,4R)-exo, stereoisomer is the preferred product.
+
<StructureSection load='1a3l' size='340' side='right'caption='[[1a3l]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1a3l]] is a 2 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=1A3L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1A3L 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]] 1.95&#8491;</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=1a3l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a3l OCA], [https://pdbe.org/1a3l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1a3l RCSB], [https://www.ebi.ac.uk/pdbsum/1a3l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1a3l ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/IGKC_MOUSE IGKC_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/a3/1a3l_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=1a3l ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
A highly specific Diels-Alder protein catalyst was made by manipulating the antibody repertoire of the immune system. The catalytic antibody 13G5 catalyzes a disfavored exo Diels-Alder transformation in a reaction for which there is no natural enzyme counterpart and that yields a single regioisomer in high enantiomeric excess. The crystal structure of the antibody Fab in complex with a ferrocenyl inhibitor containing the essential haptenic core that elicited 13G5 was determined at 1.95 angstrom resolution. Three key antibody residues appear to be responsible for the observed catalysis and product control. Tyrosine-L36 acts as a Lewis acid activating the dienophile for nucleophilic attack, and asparagine-L91 and aspartic acid-H50 form hydrogen bonds to the carboxylate side chain that substitutes for the carbamate diene substrate. This hydrogen-bonding scheme leads to rate acceleration and also pronounced stereoselectivity. Docking experiments with the four possible ortho transition states of the reaction explain the specific exo effect and suggest that the (3R,4R)-exo stereoisomer is the preferred product.
-
==About this Structure==
+
An antibody exo Diels-Alderase inhibitor complex at 1.95 angstrom resolution.,Heine A, Stura EA, Yli-Kauhaluoma JT, Gao C, Deng Q, Beno BR, Houk KN, Janda KD, Wilson IA Science. 1998 Mar 20;279(5358):1934-40. PMID:9506943<ref>PMID:9506943</ref>
-
1A3L 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 CFC as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1A3L OCA].
+
-
==Reference==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
An antibody exo Diels-Alderase inhibitor complex at 1.95 angstrom resolution., Heine A, Stura EA, Yli-Kauhaluoma JT, Gao C, Deng Q, Beno BR, Houk KN, Janda KD, Wilson IA, Science. 1998 Mar 20;279(5358):1934-40. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9506943 9506943]
+
</div>
-
[[Category: Mus musculus]]
+
<div class="pdbe-citations 1a3l" style="background-color:#fffaf0;"></div>
-
[[Category: Protein complex]]
+
-
[[Category: Heine, A.]]
+
-
[[Category: Wilson, I.A.]]
+
-
[[Category: CFC]]
+
-
[[Category: catalytic antibody]]
+
-
[[Category: diels-alder]]
+
-
[[Category: disfavored reaction]]
+
-
[[Category: immunoglobulin]]
+
-
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 18 09:25:01 2007''
+
==See Also==
 +
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Large Structures]]
 +
[[Category: Mus musculus]]
 +
[[Category: Heine A]]
 +
[[Category: Wilson IA]]

Current revision

CATALYSIS OF A DISFAVORED REACTION: AN ANTIBODY EXO DIELS-ALDERASE-TSA-INHIBITOR COMPLEX AT 1.95 A RESOLUTION

PDB ID 1a3l

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1a3l"
Personal tools