APOBEC3s: DNA-editing human cytidine deaminases

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology; Schiffer Lab

Publication Date


Document Type



Amino Acids, Peptides, and Proteins | Biochemistry | Enzymes and Coenzymes | Genetic Phenomena | Hemic and Immune Systems | Medicinal Chemistry and Pharmaceutics | Medicinal-Pharmaceutical Chemistry | Molecular Biology | Nucleic Acids, Nucleotides, and Nucleosides | Structural Biology


Nucleic acid editing enzymes are essential components of the human immune system that lethally mutate viral pathogens and somatically mutate immunoglobulins. Among these enzymes are cytidine deaminases of the apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) super family, each with unique target sequence specificity and subcellular localization. We focus on the DNA-editing APOBEC3 enzymes that have recently attracted attention because of their involvement in cancer and potential in gene-editing applications. We review and compare the crystal structures of APOBEC3 (A3) domains, binding interactions with DNA, substrate specificity, and activity. Recent crystal structures of A3A and A3G bound to ssDNA have provided insights into substrate binding and specificity determinants of these enzymes. Still many unknowns remain regarding potential cooperativity, nucleic acid interactions, and systematic quantification of substrate preference of many APOBEC3s, which are needed to better characterize the biological functions and consequences of misregulation of these gene editors.


APOBEC, DNA binding, crystal structure, cytidine deaminase, gene editing, substrate specificity

DOI of Published Version



Protein Sci. 2019 Sep;28(9):1552-1566. doi: 10.1002/pro.3670. Epub 2019 Jul 10. Link to article on publisher's site

Journal/Book/Conference Title

Protein science : a publication of the Protein Society

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Link to Article in PubMed

PubMed ID