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PDBsum entry 1c12
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Immune system
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PDB id
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1c12
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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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Insight into odorant perception: the crystal structure and binding characteristics of antibody fragments directed against the musk odorant traseolide.
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Authors
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A.C.Langedijk,
S.Spinelli,
C.Anguille,
P.Hermans,
J.Nederlof,
J.Butenandt,
A.Honegger,
C.Cambillau,
A.Plückthun.
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Ref.
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J Mol Biol, 1999,
292,
855-869.
[DOI no: ]
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PubMed id
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Abstract
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Monoclonal antibodies were elicited against the small hydrophobic hapten
traseolide, a commercially available musk fragrance. Antibody variable region
sequences were found to belong to different sequence groups, and the binding
characteristics of the corresponding antibody fragments were investigated. The
antibodies M02/01/01 and M02/05/01 are highly homologous and differ in the
binding pocket only at position H93. M02/05/01 (H93 Val) binds the hapten
traseolide about 75-fold better than M02/01/01 (H93 Ala). A traseolide analog,
missing only one methyl group, does not have the characteristic musk odorant
fragrance. The antibody M02/05/01 binds this hapten analog about tenfold less
tightly than the original traseolide hapten, and mimics the odorant receptor in
this respect, while the antibody M02/01/01 does not distinguish between the
analog and traseolide. To elucidate the structural basis for the fine
specificity of binding, we determined the crystal structure of the Fab fragment
of M02/05/01 complexed with the hapten at 2.6 A resolution. The crystal
structure showed that only van der Waals interactions are involved in binding.
The somatic Ala H93 Val mutation in M02/05/01 fills up an empty cavity in the
binding pocket. This leads to an increase in binding energy and to the ability
to discriminate between the hapten traseolide and its derivatives. The
structural understanding of odorant specificity in an antibody gives insight in
the physical principles on how specificity for such hydrophobic molecules may be
achieved.
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Figure 4.
Figure 4. Views (90 °) of the electron density map contoured at 1 sigma around the traseolide molecule and the
combining site.
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Figure 6.
Figure 6. The molecular surface of the Fab fragment
at the combining site and of the hapten. (a) View of a
molecular slice of the complex, emphasizing the non-
perfect complementarity of the surfaces. (b) Orientation
of the traseolide molecule in the combining site groove.
The surface is colored according to the curvature.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1999,
292,
855-869)
copyright 1999.
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