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PDBsum entry 1c5b
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Immune system
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PDB id
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1c5b
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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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Catalysis of decarboxylation by a preorganized heterogeneous microenvironment: crystal structures of abzyme 21d8.
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Authors
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K.Hotta,
H.Lange,
D.J.Tantillo,
K.N.Houk,
D.Hilvert,
I.A.Wilson.
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Ref.
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J Mol Biol, 2000,
302,
1213-1225.
[DOI no: ]
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PubMed id
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Abstract
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Antibody 21D8 catalyzes the solvent-sensitive decarboxylation of
3-carboxybenzisoxazoles. The crystal structure of chimeric Fab 21D8 with and
without hapten at 1.61 A and 2.10 A, respectively, together with computational
analysis, shows how a melange of polar and non-polar sites are exploited to
achieve both substrate binding and acceleration of a reaction normally
facilitated by purely aprotic dipolar media. The striking similarity of the
decarboxylase and a series of unrelated esterase antibodies also highlights the
chemical versatility of structurally conserved anion binding sites and the
relatively subtle changes involved in fine-tuning the immunoglobulin pocket for
recognition of different ligands and catalysis of different reactions.
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Figure 1.
Figure 1. Decarboxylation of 5-nitro-3-carboxybenzisoxazole
2 proceeds through a charge-delocalized transition state 3 to
give salicylonitrile 4. Naphthalene disulfonate 1 was used to
elicit the decarboxylase antibody 21D8 through a covalent
linkage to keyhole limpet hemocyanin (KLH).
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Figure 3.
Figure 3. The Fab 21D8 combining site with bound hapten.
(a) Molecular surface representation of the 21D8 binding pocket
region. Hapten sulfonate groups bind in regions that are
positively charged (blue), while the naphthalene moiety is
entirely buried within an apolar pocket (gray). (b) View of the
21D8 hapten binding site showing all the hapten-contacting
residues and their molecular interactions with the hapten. The
coloring scheme is the same as for Figure 2. (c) View of the
hapten binding pocket of the unliganded 21D8 structure, showing
the side-chain conformations of the hapten-contacting residues
and the bound water molecules (red spheres). The hapten complex
structure (darker color for Fab) is overlaid to emphasize the
position of the bound hapten (semitransparent structure) and the
slight differences in the binding site conformations.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2000,
302,
1213-1225)
copyright 2000.
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