title: Zinc enhancement of cytidine deaminase activity highlights a potential allosteric role of loop-3 in regulating APOBEC3 enzymes.
abstract: The strong association of APOBEC3 cytidine deaminases with somatic mutations leading to cancers accentuates the importance of their tight intracellular regulation to minimize cellular transformations. We reveal a novel allosteric regulatory mechanism of APOBEC3 enzymes showing that APOBEC3G and APOBEC3A coordination of a secondary zinc ion, reminiscent to ancestral deoxycytidylate deaminases, enhances deamination activity. Zinc binding is pinpointed to loop-3 which whilst highly variable harbors a catalytically essential and spatially conserved asparagine at its N-terminus. We suggest that loop-3 may play a general role in allosterically tuning the activity of zinc-dependent cytidine deaminase family members.
authors.affiliation: Faculty of Biology, Technion - Israel Institute of Technology, Haifa 320003, Israel.
authors.forename: Ailie
authors.initials: A
authors.lastname: Marx
authors.affiliation: Faculty of Biology, Technion - Israel Institute of Technology, Haifa 320003, Israel.
authors.forename: Meytal
authors.initials: M
authors.lastname: Galilee
authors.affiliation: Faculty of Biology, Technion - Israel Institute of Technology, Haifa 320003, Israel.
authors.forename: Akram
authors.initials: A
authors.lastname: Alian
mesh_terms: D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D001665:Binding Sites; D003564:Cytidine Deaminase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D016415:Sequence Alignment; D015032:Zinc / Q000378:metabolism*
chemical_list: D021122:Protein Subunits; D011994:Recombinant Proteins; D003564:Cytidine Deaminase; D015032:Zinc