Summary information and primary citation
- PDB-id
-
5zof;
SNAP-derived features in text and
JSON formats
- Class
- hydrolase-DNA
- Method
- X-ray (2.249 Å)
- Summary
- Crystal structure of d181a-r192f hfen1 in complex with
DNA
- Reference
-
Xu H, Shi R, Han W, Cheng J, Xu X, Cheng K, Wang L, Tian
B, Zheng L, Shen B, Hua Y, Zhao Y (2018): "Structural
basis of 5' flap recognition and protein-protein
interactions of human flap endonuclease 1."
Nucleic Acids Res., 46,
11315-11325. doi: 10.1093/nar/gky911.
- Abstract
- Human flap endonuclease 1 (hFEN1) is a
structure-specific nuclease essential for DNA replication
and repair processes. hFEN1 has 5' flap removal activity,
as well as gap endonuclease activity that is critical for
restarting stalled replication forks. Here, we report the
crystal structures of wild-type and mutant hFEN1 proteins
in complex with DNA substrates, followed by mutagenesis
studies that provide mechanistic insight into the
protein-protein interactions of hFEN1. We found that in an
α-helix forming the helical gateway of hFEN1 recognizes the
5' flap prior to its threading into the active site for
cleavage. We also found that the β-pin region is rigidified
into a short helix in R192F hFEN1-DNA structures,
suppressing its gap endonuclease activity and
cycle-dependent kinase interactions. Our findings suggest
that a single mutation at the primary methylation site can
alter the function of hFEN1 and provide insight into the
role of the β-pin region in hFEN1 protein interactions that
are essential for DNA replication and repair.
