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PDBsum entry 1axt
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Immunoglobulin
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PDB id
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1axt
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Immune versus natural selection: antibody aldolases with enzymic rates but broader scope.
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Authors
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C.F.Barbas,
A.Heine,
G.Zhong,
T.Hoffmann,
S.Gramatikova,
R.Björnestedt,
B.List,
J.Anderson,
E.A.Stura,
I.A.Wilson,
R.A.Lerner.
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Ref.
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Science, 1997,
278,
2085-2092.
[DOI no: ]
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PubMed id
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Abstract
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Structural and mechanistic studies show that when the selection criteria of the
immune system are changed, catalytic antibodies that have the efficiency of
natural enzymes evolve, but the catalytic antibodies are much more accepting of
a wide range of substrates. The catalytic antibodies were prepared by reactive
immunization, a process whereby the selection criteria of the immune system are
changed from simple binding to chemical reactivity. This process yielded
aldolase catalytic antibodies that approximated the rate acceleration of the
natural enzyme used in glycolysis. Unlike the natural enzyme, however, the
antibody aldolases catalyzed a variety of aldol reactions and decarboxylations.
The crystal structure of one of these antibodies identified the reactive lysine
residue that was selected in the immunization process. This lysine is deeply
buried in a hydrophobic pocket at the base of the binding site, thereby
accounting for its perturbed pKa.
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Figure 2.
Fig. 2. Comparison of the optimal reactions catalyzed by FDP
aldolase class I and the antibody aldolases. R =
4-isobutyramidobenzyl or n-butyl.
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Figure 7.
Fig. 7. Comparison of two antibody-combining sites that
contain LysH93. The environment of LysH93 is very hydrophobic in
antibody Fab  33F12 (A)
compared^ to antibody Fab 17E8 (27) (PDB code 1eap) (B).
Residues in an 8 Å sphere around LysH93N  are shown.
A space-filling CPK representation of the environment around
LysH93 is shown with hydrophobic atoms in yellow, and polar
nitrogen and oxygen atoms in cyan and salmon, respectively.
Charged basic^ residues have their nitrogen atoms colored dark
blue and charged^ oxygen atoms are colored in red. The LysH93N
atom is
colored in blue.
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The above figures are
reprinted
by permission from the AAAs:
Science
(1997,
278,
2085-2092)
copyright 1997.
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