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

Autor: Barzak FM; School of Fundamental Sciences, Massey University, Private Bag 11 222, New Zealand., Ryan TM; SAXS/WAXS, Australian Synchrotron/ANSTO, 800 Blackburn Road, Clayton, VIC 3168, Australia., Kvach MV; School of Fundamental Sciences, Massey University, Private Bag 11 222, New Zealand., Kurup HM; School of Fundamental Sciences, Massey University, Private Bag 11 222, New Zealand., Aihara H; Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA., Harris RS; Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.; Howard Hughes Medical Institute, University of Minnesota, Minneapolis, MN 55455, USA., Filichev VV; School of Fundamental Sciences, Massey University, Private Bag 11 222, New Zealand.; Maurice Wilkins Centre for Molecular Biodiscovery, Auckland 1142, New Zealand., Harjes E; School of Fundamental Sciences, Massey University, Private Bag 11 222, New Zealand.; Maurice Wilkins Centre for Molecular Biodiscovery, Auckland 1142, New Zealand., Jameson GB; School of Fundamental Sciences, Massey University, Private Bag 11 222, New Zealand.; Maurice Wilkins Centre for Molecular Biodiscovery, Auckland 1142, New Zealand.
Jazyk: angličtina
Zdroj: Viruses [Viruses] 2021 Feb 12; Vol. 13 (2). Date of Electronic Publication: 2021 Feb 12.
DOI: 10.3390/v13020290
Abstrakt: 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.
Databáze: MEDLINE
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