1eap
From Proteopedia
(New page: 200px<br /> <applet load="1eap" size="450" color="white" frame="true" align="right" spinBox="true" caption="1eap, resolution 2.4Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1eap.gif|left|200px]]<br /> | + | [[Image:1eap.gif|left|200px]]<br /><applet load="1eap" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1eap" size=" | + | |
caption="1eap, resolution 2.4Å" /> | caption="1eap, resolution 2.4Å" /> | ||
'''CRYSTAL STRUCTURE OF A CATALYTIC ANTIBODY WITH A SERINE PROTEASE ACTIVE SITE'''<br /> | '''CRYSTAL STRUCTURE OF A CATALYTIC ANTIBODY WITH A SERINE PROTEASE ACTIVE SITE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The three-dimensional structure of an unusually active hydrolytic antibody | + | The three-dimensional structure of an unusually active hydrolytic antibody with a phosphonate transition state analog (hapten) bound to the active site has been solved to 2.5 A resolution. The antibody (17E8) catalyzes the hydrolysis of norleucine and methionine phenyl esters and is selective for amino acid esters that have the natural alpha-carbon L configuration. A plot of the pH-dependence of the antibody-catalyzed reaction is bell-shaped with an activity maximum at pH 9.5; experiments on mechanism lend support to the formation of a covalent acyl-antibody intermediate. The structural and kinetic data are complementary and support a hydrolytic mechanism for the antibody that is remarkably similar to that of the serine proteases. The antibody active site contains a Ser-His dyad structure proximal to the phosphorous atom of the bound hapten that resembles two of the three components of the Ser-His-Asp catalytic triad of serine proteases. The antibody active site also contains a Lys residue to stabilize oxyanion formation, and a hydrophobic binding pocket for specific substrate recognition of norleucine and methionine side chains. The structure identifies active site residues that mediate catalysis and suggests specific mutations that may improve the catalytic efficiency of the antibody. This high resolution structure of a catalytic antibody-hapten complex shows that antibodies can converge on active site structures that have arisen through natural enzyme evolution. |
==About this Structure== | ==About this Structure== | ||
| - | 1EAP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with HEP as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1EAP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=HEP:'>HEP</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EAP OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Fletterick, R | + | [[Category: Fletterick, R J.]] |
[[Category: Guo, J.]] | [[Category: Guo, J.]] | ||
[[Category: Huang, W.]] | [[Category: Huang, W.]] | ||
| - | [[Category: Scanlan, T | + | [[Category: Scanlan, T S.]] |
| - | [[Category: Zhou, G | + | [[Category: Zhou, G W.]] |
[[Category: HEP]] | [[Category: HEP]] | ||
[[Category: catalytic antibody]] | [[Category: catalytic antibody]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:25:46 2008'' |
Revision as of 10:25, 21 February 2008
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CRYSTAL STRUCTURE OF A CATALYTIC ANTIBODY WITH A SERINE PROTEASE ACTIVE SITE
Overview
The three-dimensional structure of an unusually active hydrolytic antibody with a phosphonate transition state analog (hapten) bound to the active site has been solved to 2.5 A resolution. The antibody (17E8) catalyzes the hydrolysis of norleucine and methionine phenyl esters and is selective for amino acid esters that have the natural alpha-carbon L configuration. A plot of the pH-dependence of the antibody-catalyzed reaction is bell-shaped with an activity maximum at pH 9.5; experiments on mechanism lend support to the formation of a covalent acyl-antibody intermediate. The structural and kinetic data are complementary and support a hydrolytic mechanism for the antibody that is remarkably similar to that of the serine proteases. The antibody active site contains a Ser-His dyad structure proximal to the phosphorous atom of the bound hapten that resembles two of the three components of the Ser-His-Asp catalytic triad of serine proteases. The antibody active site also contains a Lys residue to stabilize oxyanion formation, and a hydrophobic binding pocket for specific substrate recognition of norleucine and methionine side chains. The structure identifies active site residues that mediate catalysis and suggests specific mutations that may improve the catalytic efficiency of the antibody. This high resolution structure of a catalytic antibody-hapten complex shows that antibodies can converge on active site structures that have arisen through natural enzyme evolution.
About this Structure
1EAP is a Single protein structure of sequence from Mus musculus with as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structure of a catalytic antibody with a serine protease active site., Zhou GW, Guo J, Huang W, Fletterick RJ, Scanlan TS, Science. 1994 Aug 19;265(5175):1059-64. PMID:8066444
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