1kno
From Proteopedia
(New page: 200px<br /> <applet load="1kno" size="450" color="white" frame="true" align="right" spinBox="true" caption="1kno, resolution 3.2Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1kno.gif|left|200px]]<br /> | + | [[Image:1kno.gif|left|200px]]<br /><applet load="1kno" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1kno" size=" | + | |
caption="1kno, resolution 3.2Å" /> | caption="1kno, resolution 3.2Å" /> | ||
'''CRYSTAL STRUCTURE OF THE COMPLEX OF A CATALYTIC ANTIBODY FAB WITH A TRANSITION STATE ANALOG: STRUCTURAL SIMILARITIES IN ESTERASE-LIKE ABZYMES'''<br /> | '''CRYSTAL STRUCTURE OF THE COMPLEX OF A CATALYTIC ANTIBODY FAB WITH A TRANSITION STATE ANALOG: STRUCTURAL SIMILARITIES IN ESTERASE-LIKE ABZYMES'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The x-ray structure of the complex of a catalytic antibody Fab fragment | + | The x-ray structure of the complex of a catalytic antibody Fab fragment with a phosphonate transition-state analog has been determined. The antibody (CNJ206) catalyzes the hydrolysis of p-nitrophenyl esters with significant rate enhancement and substrate specificity. Comparison of this structure with that of the uncomplexed Fab fragment suggests hapten-induced conformational changes: the shape of the combining site changes from a shallow groove in the uncomplexed Fab to a deep pocket where the hapten is buried. Three hydrogen-bond donors appear to stabilize the charged phosphonate group of the hapten: two NH groups of the heavy (H) chain complementarity-determining region 3 (H3 CDR) polypeptide chain and the side-chain of histidine-H35 in the H chain (His-H35) in the H1 CDR. The combining site shows striking structural similarities to that of antibody 17E8, which also has esterase activity. Both catalytic antibody ("abzyme") structures suggest that oxyanion stabilization plays a significant role in their rate acceleration. Additional catalytic groups that improve efficiency are not necessarily induced by the eliciting hapten; these groups may occur because of the variability in the combining sites of different monoclonal antibodies that bind to the same hapten. |
==About this Structure== | ==About this Structure== | ||
| - | 1KNO 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 ZN and PNP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1KNO 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=ZN:'>ZN</scene> and <scene name='pdbligand=PNP:'>PNP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KNO OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Charbonnier, J | + | [[Category: Charbonnier, J B.]] |
[[Category: Gigant, B.]] | [[Category: Gigant, B.]] | ||
[[Category: Knossow, M.]] | [[Category: Knossow, M.]] | ||
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[[Category: catalytic antibody]] | [[Category: catalytic antibody]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:36:02 2008'' |
Revision as of 11:36, 21 February 2008
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CRYSTAL STRUCTURE OF THE COMPLEX OF A CATALYTIC ANTIBODY FAB WITH A TRANSITION STATE ANALOG: STRUCTURAL SIMILARITIES IN ESTERASE-LIKE ABZYMES
Overview
The x-ray structure of the complex of a catalytic antibody Fab fragment with a phosphonate transition-state analog has been determined. The antibody (CNJ206) catalyzes the hydrolysis of p-nitrophenyl esters with significant rate enhancement and substrate specificity. Comparison of this structure with that of the uncomplexed Fab fragment suggests hapten-induced conformational changes: the shape of the combining site changes from a shallow groove in the uncomplexed Fab to a deep pocket where the hapten is buried. Three hydrogen-bond donors appear to stabilize the charged phosphonate group of the hapten: two NH groups of the heavy (H) chain complementarity-determining region 3 (H3 CDR) polypeptide chain and the side-chain of histidine-H35 in the H chain (His-H35) in the H1 CDR. The combining site shows striking structural similarities to that of antibody 17E8, which also has esterase activity. Both catalytic antibody ("abzyme") structures suggest that oxyanion stabilization plays a significant role in their rate acceleration. Additional catalytic groups that improve efficiency are not necessarily induced by the eliciting hapten; these groups may occur because of the variability in the combining sites of different monoclonal antibodies that bind to the same hapten.
About this Structure
1KNO is a Protein complex structure of sequences from Mus musculus with and as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structure of the complex of a catalytic antibody Fab fragment with a transition state analog: structural similarities in esterase-like catalytic antibodies., Charbonnier JB, Carpenter E, Gigant B, Golinelli-Pimpaneau B, Eshhar Z, Green BS, Knossow M, Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11721-5. PMID:8524836
Page seeded by OCA on Thu Feb 21 13:36:02 2008
