1989
DOI: 10.1073/pnas.86.14.5532
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Abstract: To study the molecular basis for antibody diversity and the structural basis for antigen binding, we have characterized the loss of phosphocholine (P-Cho) binding both experimentally and computationally in U1O, a somatic mutant of the antibody S107. Nudeotide sequencing of U10 shows a single base change in JH1, substituting As101 with Ala, over 9 A distant from the P-Cho-binding pocket. Probing with antiidiotypic antibodies suggests local, not global, conformational changes. Computational results support a spe… Show more

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Cited by 48 publications
(24 citation statements)
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“…The activity and stability of Greek-key 3-barrel proteins, such as HSOD, are strongly determined by the loops joining the P-strand framework. Loops have been categorized by structural patterns (35), and roles of individual residues in controlling antibody loop conformations have been identified (36,37). The present results identify 14 sequence-conserved, structurally consistent residues that form multiple side-chain to main-chain hydrogen bonds critical for HSOD active-site stereochemistry, for local loop conformations, and for the stable connection of different structural elements.…”
mentioning
confidence: 87%
“…The activity and stability of Greek-key 3-barrel proteins, such as HSOD, are strongly determined by the loops joining the P-strand framework. Loops have been categorized by structural patterns (35), and roles of individual residues in controlling antibody loop conformations have been identified (36,37). The present results identify 14 sequence-conserved, structurally consistent residues that form multiple side-chain to main-chain hydrogen bonds critical for HSOD active-site stereochemistry, for local loop conformations, and for the stable connection of different structural elements.…”
mentioning
confidence: 87%
“…Nevertheless, there are numerous data demonstrating the importance of this structural element in ligand binding (17,18,(42)(43)(44)(45). Despite the alteration of charged residues to alanine (that was accompanied with a dramatic change in the nature of the side chain group), all mutations directed to the base of HCDR3 influenced affinity less than those directed to the predicted top of the loop (Table III) A similar conclusion follows from the analysis of changes in ⌬G°of binding in comparison with DNA-1 (⌬⌬G°) induced by the three mutations formed in "the double mutant cycle" (Table III).…”
Section: Measurement Of Affinities Of Hcdr3 Mutants By Equilibrium Flmentioning
confidence: 99%
“…The possibility that mutated residues are actually in contact with the antigen epitope(s) in the antibody-antigen complex structure should be investigated further using techniques, such as site-directed mutagenesis and molecular modeling. In the case of protein antigens, it has not yet been known that somatic mutations distal from the contact sites of antibodies have a functional role, although somatic hypermutations occurred in non-contact residues of antibodies for small haptenic antigens (Chien et al, 1989;Strong et al, 1991;Patten et al, 1996).…”
Section: Discussionmentioning
confidence: 99%