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The load of structural evidence favors the concept that an ATP-dependent ligase may be the ancestral condition from which NAD+-dependent ligases developed, by acquisition of a specialised structural area (Ia) that binds the NMN leaving team. All regarded NAD+-dependent ligases have domain Ia, and they can't use ATP to be a substrate for ligase adenylylation, presumably simply because LigA enzymes absence “motif IV” of the OB domain, the component of ATP-dependent DNA ligases that is thought to interact with the PPi leaving team of ATP (five, 19). This “either/or” situation of DNA ligase substrate specificity has been roiled by numerous seemingly conflicting reviews in regards to the nucleotide specificity of archaeal DNA ligases.
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