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It is suggested that the divergent clade ShHTLs lost the ability to bind to KAR due to bulky residue 219, and they developed a highly sensitive subgroup (ShHTL4, ShHTL5, and ShHTL7) for SL binding likely via the evolution of F150 and other pocket-composing residues (e.g., residue 194)

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Drugs such as MetanX, Deplin, and CerefolinNAC contain methyl folate and may be beneficial