5ZOD

Crystal Structure of hFen1 in apo form

Summary for 5ZOD

• Entry DOI: 10.2210/pdb5zod/pdb
• Related: 5UM9
• Descriptor: Flap endonuclease 1, MAGNESIUM ION, POTASSIUM ION, ... (4 entities in total)
• Functional Keywords: flap endonuclease: gap endonuclease: methylation: posttranslational modification, dna binding protein, hydrolase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 37872.29

Authors

Han, W.,Hua, Y.,Zhao, Y. (deposition date: 2018-04-13, release date: 2019-01-30, Last modification date: 2023-11-22)

Primary citation

Xu, H.,Shi, R.,Han, W.,Cheng, J.,Xu, X.,Cheng, K.,Wang, L.,Tian, B.,Zheng, L.,Shen, B.,Hua, Y.,Zhao, Y.
Structural basis of 5' flap recognition and protein-protein interactions of human flap endonuclease 1.
Nucleic Acids Res., 46:11315-11325, 2018

PubMed 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.

PubMed: 30295841
DOI: 10.1093/nar/gky911

Experimental method

X-RAY DIFFRACTION (1.9 Å)