1a3l
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1a3l.gif|left|200px]] | [[Image:1a3l.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1a3l", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | | | + | or leave the SCENE parameter empty for the default display. |
| - | | | + | --> |
| - | + | {{STRUCTURE_1a3l| PDB=1a3l | SCENE= }} | |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''CATALYSIS OF A DISFAVORED REACTION: AN ANTIBODY EXO DIELS-ALDERASE-TSA-INHIBITOR COMPLEX AT 1.95 A RESOLUTION''' | '''CATALYSIS OF A DISFAVORED REACTION: AN ANTIBODY EXO DIELS-ALDERASE-TSA-INHIBITOR COMPLEX AT 1.95 A RESOLUTION''' | ||
| Line 27: | Line 24: | ||
[[Category: Heine, A.]] | [[Category: Heine, A.]] | ||
[[Category: Wilson, I A.]] | [[Category: Wilson, I A.]] | ||
| - | [[Category: | + | [[Category: Catalytic antibody]] |
| - | [[Category: | + | [[Category: Diels-alder]] |
| - | [[Category: | + | [[Category: Disfavored reaction]] |
| - | [[Category: | + | [[Category: Immunoglobulin]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 09:45:45 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 06:45, 2 May 2008
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. 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 Fri May 2 09:45:45 2008
