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Figure 5
Substitutions of leucine at position 5, shown in stereo and superimposed on the cQFD meditope (green C atoms). (a) The leucine side chain resides in a hydrophobic pocket defined by Thr90 (T90), Ile92 (I92) and Leu114 (L114) of the Fab heavy chain and Pro40 (P40) of the Fab light chain. (b) Substitution of leucine with tyrosine in the meditope positions the hydroxyl group near the side chain of Glu154 (E154) and the hydroxyl group of Tyr182 (Y182). (c) The replacement of leucine with glutamine at position 5 was intended to create a hydrogen bond to the hydroxyl group of Y182 in the heavy chain or the hydroxyl of T90 in the light chain. However, the side chain points away from the Fab. (d) Substitution with glutamic acid resulted in positioning of the carboxylic acid in the hydrophobic pocket. The high B factors of the carboxylate suggest that the positioning of the side chain is adventitious. (e) Substitution at position 5 with diphenylalanine places one phenyl group at the same position as the leucine side chain. The other phenyl group extends further into the meditope cavity that is lined with the hydrophobic residues.

ISSN: 2053-230X
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