3Q8K

Crystal Structure of Human Flap Endonuclease FEN1 (WT) in complex with product 5'-flap DNA, SM3+, and K+

3Q8K の概要

• エントリーDOI: 10.2210/pdb3q8k/pdb
• 関連するPDBエントリー: 3Q8L 3Q8M
• 分子名称: Flap endonuclease 1, DNA (5'-D(*AP*CP*TP*CP*TP*GP*CP*CP*TP*CP*AP*AP*GP*AP*CP*GP*GP*T)-3'), DNA (5'-D(P*TP*GP*AP*GP*GP*CP*AP*GP*AP*GP*T)-3'), ... (8 entities in total)
• 機能のキーワード: helix-3 turn-helix, hydrophobic wedge, 3' flap binding site, hydrolase-dna complex, dna repair, replication, flap endonuclease, fen, fen1, dna, nuclease, 5' flap, ss-dsdna junction, helix-2 turn-helix, h2th, h3th, divalent cation, helical gateway, cap, acid block, two metal mechanism, unpaired, 5' nuclease, human, long patch base excision repair, hydrolase/dna
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus, nucleolus: P39748
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 50141.92

構造登録者

Tsutakawa, S.E.,Classen, S.,Chapados, B.R.,Arvai, A.,Finger, D.L.,Guenther, G.,Tomlinson, C.G.,Thompson, P.,Sarker, A.H.,Shen, B.,Cooper, P.K.,Grasby, J.A.,Tainer, J.A. (登録日: 2011-01-06, 公開日: 2011-04-27, 最終更新日: 2023-09-13)

主引用文献

Tsutakawa, S.E.,Classen, S.,Chapados, B.R.,Arvai, A.S.,Finger, L.D.,Guenther, G.,Tomlinson, C.G.,Thompson, P.,Sarker, A.H.,Shen, B.,Cooper, P.K.,Grasby, J.A.,Tainer, J.A.
Human Flap Endonuclease Structures, DNA Double-Base Flipping, and a Unified Understanding of the FEN1 Superfamily.
Cell(Cambridge,Mass.), 145:198-211, 2011

PubMed Abstract: Flap endonuclease (FEN1), essential for DNA replication and repair, removes RNA and DNA 5' flaps. FEN1 5' nuclease superfamily members acting in nucleotide excision repair (XPG), mismatch repair (EXO1), and homologous recombination (GEN1) paradoxically incise structurally distinct bubbles, ends, or Holliday junctions, respectively. Here, structural and functional analyses of human FEN1:DNA complexes show structure-specific, sequence-independent recognition for nicked dsDNA bent 100° with unpaired 3' and 5' flaps. Above the active site, a helical cap over a gateway formed by two helices enforces ssDNA threading and specificity for free 5' ends. Crystallographic analyses of product and substrate complexes reveal that dsDNA binding and bending, the ssDNA gateway, and double-base unpairing flanking the scissile phosphate control precise flap incision by the two-metal-ion active site. Superfamily conserved motifs bind and open dsDNA; direct the target region into the helical gateway, permitting only nonbase-paired oligonucleotides active site access; and support a unified understanding of superfamily substrate specificity.

PubMed: 21496641
DOI: 10.1016/j.cell.2011.03.004

実験手法

X-RAY DIFFRACTION (2.2001 Å)