1y18: Difference between revisions

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[[Image:1y18.gif|left|200px]]<br />

[[Image:1y18.gif|left|200px]]<br /><applet load="1y18" size="350" color="white" frame="true" align="right" spinBox="true"

<applet load="1y18" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="1y18, resolution 2.80Å" />

'''Fab fragment of catalytic elimination antibody 34E4 E(H50)D mutant in complex with hapten'''<br />

==Overview==

Antibody 34E4 catalyzes the conversion of benzisoxazoles to, salicylonitriles with high rates and multiple turnovers. The crystal, structure of its complex with the benzimidazolium hapten at 2.5-angstroms, resolution shows that a combination of hydrogen bonding, pi stacking, and, van der Waals interactions is exploited to position both the base, Glu(H50), and the substrate for efficient proton transfer. Suboptimal, placement of the catalytic carboxylate, as observed in the 2.8-angstroms, structure of the Glu(H50)Asp variant, results in substantially reduced, catalytic efficiency. In addition to imposing high positional order on the, transition state, the antibody pocket provides a highly structured, microenvironment for the reaction in which the carboxylate base is, activated through partial desolvation, and the highly polarizable, transition state is stabilized by dispersion interactions with the, aromatic residue Trp(L91) and solvation of the leaving group oxygen by, external water. The enzyme-like efficiency of general base catalysis in, this system directly reflects the original hapten design, in which a, charged guanidinium moiety was strategically used to elicit an accurately, positioned functional group in an appropriate reaction environment and, suggests that even larger catalytic effects may be achievable by extending, this approach to the induction of acid-base pairs capable of bifunctional, catalysis.

Antibody 34E4 catalyzes the conversion of benzisoxazoles to salicylonitriles with high rates and multiple turnovers. The crystal structure of its complex with the benzimidazolium hapten at 2.5-angstroms resolution shows that a combination of hydrogen bonding, pi stacking, and van der Waals interactions is exploited to position both the base, Glu(H50), and the substrate for efficient proton transfer. Suboptimal placement of the catalytic carboxylate, as observed in the 2.8-angstroms structure of the Glu(H50)Asp variant, results in substantially reduced catalytic efficiency. In addition to imposing high positional order on the transition state, the antibody pocket provides a highly structured microenvironment for the reaction in which the carboxylate base is activated through partial desolvation, and the highly polarizable transition state is stabilized by dispersion interactions with the aromatic residue Trp(L91) and solvation of the leaving group oxygen by external water. The enzyme-like efficiency of general base catalysis in this system directly reflects the original hapten design, in which a charged guanidinium moiety was strategically used to elicit an accurately positioned functional group in an appropriate reaction environment and suggests that even larger catalytic effects may be achievable by extending this approach to the induction of acid-base pairs capable of bifunctional catalysis.

==About this Structure==

1Y18 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus,_homo_sapiens Mus musculus, homo sapiens] with CL and HAN as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1Y18 OCA].

1Y18 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus,_homo_sapiens Mus musculus, homo sapiens] with <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=HAN:'>HAN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y18 OCA].

==Reference==

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Line 13:

[[Category: Mus musculus, homo sapiens]]

[[Category: Protein complex]]

[[Category: Debler, E.W.]]

[[Category: Debler, E W.]]

[[Category: Heine, A.]]

[[Category: Ito, S.]]

[[Category: Wilson, I.A.]]

[[Category: Wilson, I A.]]

[[Category: CL]]

[[Category: HAN]]

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[[Category: immunoglobulin]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Sun Nov 18 09~~:44:~~59 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:00:46 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1y18.gif|left|200px]]<br />
+[[Image:1y18.gif|left|200px]]<br /><applet load="1y18" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1y18" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1y18, resolution 2.80&Aring;" />
 '''Fab fragment of catalytic elimination antibody 34E4 E(H50)D mutant in complex with hapten'''<br />
 ==Overview==
-Antibody 34E4 catalyzes the conversion of benzisoxazoles to, salicylonitriles with high rates and multiple turnovers. The crystal, structure of its complex with the benzimidazolium hapten at 2.5-angstroms, resolution shows that a combination of hydrogen bonding, pi stacking, and, van der Waals interactions is exploited to position both the base, Glu(H50), and the substrate for efficient proton transfer. Suboptimal, placement of the catalytic carboxylate, as observed in the 2.8-angstroms, structure of the Glu(H50)Asp variant, results in substantially reduced, catalytic efficiency. In addition to imposing high positional order on the, transition state, the antibody pocket provides a highly structured, microenvironment for the reaction in which the carboxylate base is, activated through partial desolvation, and the highly polarizable, transition state is stabilized by dispersion interactions with the, aromatic residue Trp(L91) and solvation of the leaving group oxygen by, external water. The enzyme-like efficiency of general base catalysis in, this system directly reflects the original hapten design, in which a, charged guanidinium moiety was strategically used to elicit an accurately, positioned functional group in an appropriate reaction environment and, suggests that even larger catalytic effects may be achievable by extending, this approach to the induction of acid-base pairs capable of bifunctional, catalysis.
+Antibody 34E4 catalyzes the conversion of benzisoxazoles to salicylonitriles with high rates and multiple turnovers. The crystal structure of its complex with the benzimidazolium hapten at 2.5-angstroms resolution shows that a combination of hydrogen bonding, pi stacking, and van der Waals interactions is exploited to position both the base, Glu(H50), and the substrate for efficient proton transfer. Suboptimal placement of the catalytic carboxylate, as observed in the 2.8-angstroms structure of the Glu(H50)Asp variant, results in substantially reduced catalytic efficiency. In addition to imposing high positional order on the transition state, the antibody pocket provides a highly structured microenvironment for the reaction in which the carboxylate base is activated through partial desolvation, and the highly polarizable transition state is stabilized by dispersion interactions with the aromatic residue Trp(L91) and solvation of the leaving group oxygen by external water. The enzyme-like efficiency of general base catalysis in this system directly reflects the original hapten design, in which a charged guanidinium moiety was strategically used to elicit an accurately positioned functional group in an appropriate reaction environment and suggests that even larger catalytic effects may be achievable by extending this approach to the induction of acid-base pairs capable of bifunctional catalysis.
 ==About this Structure==
-Y18 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus,_homo_sapiens Mus musculus, homo sapiens] with CL and HAN as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1Y18 OCA].
+Y18 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus,_homo_sapiens Mus musculus, homo sapiens] with <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=HAN:'>HAN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y18 OCA].
 ==Reference==
@@ Line 14: / Line 13: @@
 [[Category: Mus musculus, homo sapiens]]
 [[Category: Protein complex]]
-[[Category: Debler, E.W.]]
+[[Category: Debler, E W.]]
 [[Category: Heine, A.]]
 [[Category: Ito, S.]]
-[[Category: Wilson, I.A.]]
+[[Category: Wilson, I A.]]
 [[Category: CL]]
 [[Category: HAN]]
@@ Line 25: / Line 24: @@
 [[Category: immunoglobulin]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 18 09:44:59 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:00:46 2008''