1c12
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| , resolution 2.60Å | |||||||
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| Ligands: | |||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
INSIGHT IN ODORANT PERCEPTION: THE CRYSTAL STRUCTURE AND BINDING CHARACTERISTICS OF ANTIBODY FRAGMENTS DIRECTED AGAINST THE MUSK ODORANT TRASEOLIDE
OverviewOverview
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.
About this StructureAbout this Structure
1C12 is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.
ReferenceReference
Insight into odorant perception: the crystal structure and binding characteristics of antibody fragments directed against the musk odorant traseolide., Langedijk AC, Spinelli S, Anguille C, Hermans P, Nederlof J, Butenandt J, Honegger A, Cambillau C, Pluckthun A, J Mol Biol. 1999 Oct 1;292(4):855-69. PMID:10525411
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