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Computational structural analysis of an anti‐ L ‐amino acid antibody and inversion of its stereoselectivity
Author(s) -
Ranieri Daniel I.,
Hofstetter Heike,
Hofstetter Oliver
Publication year - 2009
Publication title -
journal of separation science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.72
H-Index - 102
eISSN - 1615-9314
pISSN - 1615-9306
DOI - 10.1002/jssc.200800694
Subject(s) - chemistry , steric effects , amino acid , stereoselectivity , enantiomer , complementarity determining region , stereochemistry , phenylalanine , docking (animal) , antibody , hydrogen bond , biochemistry , peptide sequence , molecule , organic chemistry , biology , genetics , medicine , nursing , gene , catalysis
The binding site of a monoclonal anti‐ L ‐amino acid antibody (anti‐ L ‐AA) was modeled using the program SWISS‐MODEL. Docking experiments with the enantiomers of phenylalanine revealed that the antibody interacts with L ‐phenylalanine via hydrogen bonds and hydrophobic contacts, whereas the D ‐enantiomer is rejected due to steric hindrance. Comparison of the sequences of this antibody and an anti‐ D ‐amino acid antibody (anti‐ D ‐AA) indicates that both immunoglobulins derived from the same germline progenitor. Substitution of four amino acids residues, three in the framework and one in the complementarity determining regions (CDRs), allowed in silico conversion of the anti‐ L ‐AA into an antibody that stereoselectively binds D ‐phenylalanine.