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Creating more space in the active site of the tryptophan 7-halogenase PrnA by exchanging the large amino acid phenylalanine for the smaller alanine makes it possible for the substrate to bind in different orientations (see picture; yellow PrnA, blue PrnAF103A variant). This results in halogenation of the differently bound substrate in the 5-position of the indole ring.
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Lang et al. (2011) studied this question.
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