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Title
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Differences in the biochemical properties of esterolytic antibodies correlate with structural diversity.
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Authors
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R.Zemel,
D.G.Schindler,
D.S.Tawfik,
Z.Eshhar,
B.S.Green.
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Ref.
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Mol Immunol, 1994,
31,
127-137.
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PubMed id
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Abstract
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A prerequisite to the design and engineering of catalytic antibodies is the
knowledge of their structure and in particular which residues are involved in
binding and catalysis. We compared the structure and catalytic properties of a
series of six monoclonal antibodies which were all raised against a
p-nitrophenyl (PNP) phosphonate and which catalyze the hydrolysis of
p-nitrophenyl esters. Three of the antibodies (Group I) have similar light and
heavy chain variable regions. The other three antibodies have similar VL regions
of which two (Group II) have VH regions from the MOPC21 gene family and the
remaining one (Group III) a VH from the MC101 gene family making a total of
three different groups based on their V region sequences. The structural
division into groups is paralleled by the differences in binding constants to
hapten analogs, substrate specificity and the susceptibility of the catalytic
activity of the antibodies to chemical modification of tryptophan and arginine
residues. The relative binding of a transition state analog to the binding of
substrate is much higher for the Group I antibodies than for the other groups.
Only the Group I antibodies can catalyze the hydrolysis of a carbonate
substrate. However all of the antibodies lose catalytic activity upon specific
tyrosine modification which highlights the importance of tyrosine in the active
site of the antibodies. Thus, antibodies raised against a single hapten can give
antibodies with different structures, and correspondingly different
specificities and catalytic properties.
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