2gfb: Difference between revisions

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CRYSTAL STRUCTURE OF A CATALYTIC FAB HAVING ESTERASE-LIKE ACTIVITY

OverviewOverview

BACKGROUND: Antibodies with catalytic properties can be prepared by eliciting an antibody response against 'transition state analog' haptens. The specificity, rate and number of reaction cycles observed with these antibodies more closely resemble the properties of enzymes than any of the many other known enzyme-mimicking systems. RESULTS: We have determined to 3 A resolution the first X-ray structure of a catalytic antibody Fab. This antibody catalyzes the hydrolysis of a p-nitrophenyl ester. In conjunction with binding studies in solution, this structure of the uncomplexed site suggests a model for transition state fixation where two tyrosines mimic the oxyanion binding hole of serine proteases. A comparison with the structures of known Fabs specific for low molecular weight haptens reveals that this catalytic antibody has an unusually long groove at its combining site. CONCLUSION: Since transition state analogs contain elements of the desired product, product inhibition is a severe problem in antibody catalysis. The observation of a long groove at the combining site may relate to the ability of this catalytic antibody to achieve multiple cycles of reaction.

About this StructureAbout this Structure

2GFB is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of a catalytic antibody Fab with esterase-like activity., Golinelli-Pimpaneau B, Gigant B, Bizebard T, Navaza J, Saludjian P, Zemel R, Tawfik DS, Eshhar Z, Green BS, Knossow M, Structure. 1994 Mar 15;2(3):175-83. PMID:8069632

Page seeded by OCA on Thu Feb 21 17:31:06 2008

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OCA

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-[[Image:2gfb.gif|left|200px]]<br />
+[[Image:2gfb.gif|left|200px]]<br /><applet load="2gfb" size="350" color="white" frame="true" align="right" spinBox="true"
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 caption="2gfb, resolution 3.0&Aring;" />
 '''CRYSTAL STRUCTURE OF A CATALYTIC FAB HAVING ESTERASE-LIKE ACTIVITY'''<br />
 ==Overview==
-BACKGROUND: Antibodies with catalytic properties can be prepared by, eliciting an antibody response against 'transition state analog' haptens., The specificity, rate and number of reaction cycles observed with these, antibodies more closely resemble the properties of enzymes than any of the, many other known enzyme-mimicking systems. RESULTS: We have determined to, 3 A resolution the first X-ray structure of a catalytic antibody Fab. This, antibody catalyzes the hydrolysis of a p-nitrophenyl ester. In conjunction, with binding studies in solution, this structure of the uncomplexed site, suggests a model for transition state fixation where two tyrosines mimic, the oxyanion binding hole of serine proteases. A comparison with the, structures of known Fabs specific for low molecular weight haptens reveals, that this catalytic antibody has an unusually long groove at its combining, site. CONCLUSION: Since transition state analogs contain elements of the, desired product, product inhibition is a severe problem in antibody, catalysis. The observation of a long groove at the combining site may, relate to the ability of this catalytic antibody to achieve multiple, cycles of reaction.
+BACKGROUND: Antibodies with catalytic properties can be prepared by eliciting an antibody response against 'transition state analog' haptens. The specificity, rate and number of reaction cycles observed with these antibodies more closely resemble the properties of enzymes than any of the many other known enzyme-mimicking systems. RESULTS: We have determined to 3 A resolution the first X-ray structure of a catalytic antibody Fab. This antibody catalyzes the hydrolysis of a p-nitrophenyl ester. In conjunction with binding studies in solution, this structure of the uncomplexed site suggests a model for transition state fixation where two tyrosines mimic the oxyanion binding hole of serine proteases. A comparison with the structures of known Fabs specific for low molecular weight haptens reveals that this catalytic antibody has an unusually long groove at its combining site. CONCLUSION: Since transition state analogs contain elements of the desired product, product inhibition is a severe problem in antibody catalysis. The observation of a long groove at the combining site may relate to the ability of this catalytic antibody to achieve multiple cycles of reaction.
 ==About this Structure==
-GFB is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2GFB OCA].
+GFB is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GFB OCA].
 ==Reference==
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 [[Category: immunoglobulin]]
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