Structural basis of substrate specificity in human cytidine deaminase family APOBEC3s
Shurong Hou, Jeong Min Lee, Wazo Myint, Hiroshi Matsuo, Neşe Kurt Yılmaz, Celia A. Schiffer
Abstract
motif when ssDNA is in a more linear (L) conformation. A3B can also bind both U- and L-shaped ssDNA, unlike A3G, which can stably recognize only linear ssDNA. These varied conformations are stabilized by sequence-specific interactions with active site loops 1 and 7, which are highly variable among A3s. Our results explain the molecular basis of previously observed substrate specificities in A3s and have implications for designing A3-specific inhibitors for cancer therapy as well as engineering base-editing systems for gene therapy.
Topics & Concepts
Cytidine deaminaseActivation-induced (cytidine) deaminaseCytidineNucleotideActive siteSequence motifAPOBECBiologyChemistryDNAGeneComputational biologyStereochemistryBiochemistryEnzymeGeneticsImmunoglobulin class switchingB cellAntibodyGenomeCRISPR and Genetic EngineeringRNA and protein synthesis mechanismsMonoclonal and Polyclonal Antibodies Research