Small-Angle X-ray Scattering Models of APOBEC3B Catalytic Domain in a Complex with a Single-Stranded DNA Inhibitor

Fareeda M. Barzak, Timothy M. Ryan, Maksim V. Kvach, Harikrishnan M. Kurup, Hideki Aihara, Reuben S. Harris, Vyacheslav V. Filichev, Elena Harjes, Geoffrey B. Jameson

Research output: Contribution to journalArticlepeer-review


In normal cells APOBEC3 (A3A-A3H) enzymes as part of the innate immune system deaminate cytosine to uracil on single-stranded DNA (ssDNA) to scramble DNA in order to give protection against a range of exogenous retroviruses, DNA-based parasites, and endogenous retroelements. However, some viruses and cancer cells use these enzymes, especially A3A and A3B, to escape the adaptive immune response and thereby lead to the evolution of drug resistance. We have synthesized first-in-class inhibitors featuring modified ssDNA. We present models based on small-angle X-ray scattering (SAXS) data that (1) confirm that the mode of binding of inhibitor to an active A3B C-terminal domain construct in the solution state is the same as the mode of binding substrate to inactive mutants of A3A and A3B revealed in X-ray crystal structures and (2) give insight into the disulfide-linked inactive dimer formed under the oxidizing conditions of purification.

Original languageEnglish (US)
Issue number2
StatePublished - Feb 12 2021

Bibliographical note

This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine


  • APOBEC inhibitors
  • cancer evolution
  • dimer
  • drug resistance
  • SAXS
  • virus restriction

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

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