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The weight of structural proof favors the concept that an ATP-dependent ligase would be the ancestral state from which NAD+-dependent ligases evolved, by acquisition of a specialized structural domain (Ia) that binds the NMN leaving team. All known NAD+-dependent ligases have area Ia, and they cannot use ATP to be a substrate for ligase adenylylation, presumably simply because LigA enzymes deficiency “motif IV” in the OB area, the component of ATP-dependent DNA ligases that is believed to interact with the PPi leaving group of ATP (5, 19). This “possibly/or” situation of DNA ligase substrate specificity continues to be roiled by quite a few seemingly conflicting studies concerning the nucleotide specificity of archaeal DNA ligases.
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