1a3l
From Proteopedia
(New page: 200px<br /> <applet load="1a3l" size="450" color="white" frame="true" align="right" spinBox="true" caption="1a3l, resolution 1.95Å" /> '''CATALYSIS OF A DISF...) |
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| - | [[Image:1a3l.gif|left|200px]]<br /> | + | [[Image:1a3l.gif|left|200px]]<br /><applet load="1a3l" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1a3l, resolution 1.95Å" /> | caption="1a3l, resolution 1.95Å" /> | ||
'''CATALYSIS OF A DISFAVORED REACTION: AN ANTIBODY EXO DIELS-ALDERASE-TSA-INHIBITOR COMPLEX AT 1.95 A RESOLUTION'''<br /> | '''CATALYSIS OF A DISFAVORED REACTION: AN ANTIBODY EXO DIELS-ALDERASE-TSA-INHIBITOR COMPLEX AT 1.95 A RESOLUTION'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A highly specific Diels-Alder protein catalyst was made by manipulating | + | 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== | ==About this Structure== | ||
| - | 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:// | + | 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 <scene name='pdbligand=CFC:'>CFC</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A3L OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Heine, A.]] | [[Category: Heine, A.]] | ||
| - | [[Category: Wilson, I | + | [[Category: Wilson, I A.]] |
[[Category: CFC]] | [[Category: CFC]] | ||
[[Category: catalytic antibody]] | [[Category: catalytic antibody]] | ||
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[[Category: immunoglobulin]] | [[Category: immunoglobulin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:40:26 2008'' |
Revision as of 09:40, 21 February 2008
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CATALYSIS OF A DISFAVORED REACTION: AN ANTIBODY EXO DIELS-ALDERASE-TSA-INHIBITOR COMPLEX AT 1.95 A RESOLUTION
Overview
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
1A3L is a Protein complex structure of sequences from Mus musculus with as ligand. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 11:40:26 2008
