1axs
From Proteopedia
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| - | [[Image:1axs.gif|left|200px]]<br /><applet load="1axs" size=" | + | [[Image:1axs.gif|left|200px]]<br /><applet load="1axs" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1axs, resolution 2.6Å" /> | caption="1axs, resolution 2.6Å" /> | ||
'''MATURE OXY-COPE CATALYTIC ANTIBODY WITH HAPTEN'''<br /> | '''MATURE OXY-COPE CATALYTIC ANTIBODY WITH HAPTEN'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1AXS is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CD and HOP as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Site: <scene name='pdbsite=CAT:Hapten Binding Site'>CAT</scene>. Full crystallographic information is available from [http:// | + | 1AXS is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CD:'>CD</scene> and <scene name='pdbligand=HOP:'>HOP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Site: <scene name='pdbsite=CAT:Hapten+Binding+Site'>CAT</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AXS OCA]. |
==Reference== | ==Reference== | ||
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[[Category: oxy-cope]] | [[Category: oxy-cope]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 09:32:01 2008'' |
Revision as of 07:32, 3 February 2008
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MATURE OXY-COPE CATALYTIC ANTIBODY WITH HAPTEN
Overview
Antibody catalysis provides an opportunity to examine the evolution of, binding energy and its relation to catalytic function in a system that has, many parallels with natural enzymes. Here we report such a study involving, an antibody AZ-28 that catalyses an oxy-Cope rearrangement, a pericyclic, reaction that belongs to a well studied and widely used class of reactions, in organic chemistry. Immunization with transition state analogue 1, results in a germline-encoded antibody that catalyses the rearrangement of, hexadiene 2 to aldehyde 3 with a rate approaching that of a related, pericyclic reaction catalysed by the enzyme chorismate mutase. Affinity, maturation gives antibody AZ-28, which has six amino acid substitutions, one of which results in a decrease in catalytic rate. To understand the, relationship between binding and catalytic rate in this system we, characterized a series of active-site mutants and determined the, three-dimensional crystal structure of the complex of AZ-28 with the, transition state analogue. This analysis indicates that the activation, energy depends on a complex balance of several stereoelectronic effects, which are controlled by an extensive network of binding interactions in, the active site. Thus in this instance the combinatorial diversity of the, immune system provided both an efficient catalyst for a reaction where no, enzyme is known, as well as an opportunity to explore the mechanisms and, evolution of biological catalysis.
About this Structure
1AXS is a Protein complex structure of sequences from Homo sapiens with and as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
The interplay between binding energy and catalysis in the evolution of a catalytic antibody., Ulrich HD, Mundorff E, Santarsiero BD, Driggers EM, Stevens RC, Schultz PG, Nature. 1997 Sep 18;389(6648):271-5. PMID:9305839
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