Modeling the Embrace of a Mutator: APOBEC Selection of Nucleic Acid Ligands.

Jason D Salter, Harold C Smith

Journal: Trends in biochemical sciences 2019;43(8):606-622

PMID: 29803538

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Abstract

The 11-member APOBEC (apolipoprotein B mRNA editing catalytic polypeptide-like) family of zinc-dependent cytidine deaminases bind to RNA and single-stranded DNA (ssDNA) and, in specific contexts, modify select (deoxy)cytidines to (deoxy)uridines. In this review, we describe advances made through high-resolution co-crystal structures of APOBECs bound to mono- or oligonucleotides that reveal potential substrate-specific binding sites at the active site and non-sequence-specific nucleic acid binding sites distal to the active site. We also discuss the effect of APOBEC oligomerization on functionality. Future structural studies will need to address how ssDNA binding away from the active site may enhance catalysis and the mechanism by which RNA binding may modulate catalytic activity on ssDNA.

Address: OyaGen, Inc., 77 Ridgeland Road, Rochester, NY 14623, USA. Electronic address: [email protected].; OyaGen, Inc., 77 Ridgeland Road, Rochester, NY 14623, USA; University of Rochester, School of Medicine and Dentistry, Department of Biochemistry and Biophysics, 601 Elmwood Avenue, Rochester, NY 14642, USA. Electronic address: [email protected].

DOI: 10.1016/j.tibs.2018.04.013

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MeSH Terms: APOBEC Deaminases, Catalysis, Cytidine Deaminase, Deamination, Ligands, Models, Chemical, Mutation, Nucleic Acids, Protein Binding, Protein Folding