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The positioning of the 296 phenol suggests that in the absence of NADPH it orients to block access to the isoalloxazine N5 and prevent non-specific reduction or reoxidation of the flavin, kinetically restricting promiscuous/futile electron transfer out of the TGR population such that even low reduction potential non-native reductants fail to reduce the FAD significantly on timeframes relative to catalysis
Presented for research literature review only Anderson MF et al
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