SNAP output for PDB entry 5w2m [SNAP web server]

PDB-id

5w2m; SNAP-derived features in text and JSON formats; DNAproDB

Class

DNA binding protein

Method

X-ray (3.7 Å)

Summary

Apobec3f catalytic domain complex with a single-stranded DNA

Reference

Fang Y, Xiao X, Li SX, Wolfe A, Chen XS (2018): "Molecular Interactions of a DNA Modifying Enzyme APOBEC3F Catalytic Domain with a Single-Stranded DNA." J. Mol. Biol., 430, 87-101. doi: 10.1016/j.jmb.2017.11.007.

Abstract

The single-stranded DNA (ssDNA) cytidine deaminase APOBEC3F (A3F) deaminates cytosine (C) to uracil (U) and is a known restriction factor of HIV-1. Its C-terminal catalytic domain (CD2) alone is capable of binding single-stranded nucleic acids and is important for deamination. However, little is known about how the CD2 interacts with single-stranded DNA (ssDNA). Here we report a crystal structure of A3F-CD2 in complex with a 10 nucleotide (nt) ssDNA composed of poly-thymine, which reveals a novel positively-charged nucleic acid binding site distal to the active center that plays a key role in substrate DNA binding and catalytic activity. Lysine and tyrosine residues within this binding site interact with the ssDNA, and mutating these residues dramatically impairs both ssDNA binding and catalytic activity. This binding site is not conserved in APOBEC3G (A3G), which may explain differences in ssDNA binding characteristics between A3F-CD2 and A3G-CD2. In addition, we observed an alternative Zn-coordination conformation around the active center. These findings reveal the structural relationships between nucleic acid interactions and catalytic activity of A3F.