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The importance of R98 is likely to be explained by its interaction with the surrounding tyrosines through cation–pi interactions, most notably with one located in CDR loop three (Y111). Therefore, it is of utmost importance that this position remains an arginine in order to retain binding affinity. The “tyrosine cage” at that position could, in conjunction with R98, lead to a more restricted local environment for the CDR loop, which is shown in red.
