9RCI: Flap Endonuclease FEN1 with Compound 28

Crystal Structure of Flap Endonuclease FEN1 with Compound 28. Determined by X-ray diffraction at 1.66 Å resolution. Released 24 Sept 2025.

Method: X-ray diffraction
Resolution: 1.66 Å
Organism: Homo sapiens
Chains: 2
Atoms: 4,505
Mol. weight: 78.35 kDa
Ligands: MG, A1JD4
Released: 24 Sept 2025

Explore 9RCI in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9RCI contains 39 α-helices and 14 β-strands across 2 chains. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chain A: 19 helices, 7 β-strands

Element	Residues	Length	Sheet
α-helix	6-13	8
α-helix	15-17	3
β-strand	18-21	4	1
α-helix	23-26	4
β-strand	30-34	5	1
α-helix	35-43	9
α-helix	62-76	15
β-strand	80-85	6	1
α-helix	135-147	13
β-strand	152-154	3	1
α-helix	159-168	10
β-strand	174-176	3	1
α-helix	181-184	4
β-strand	189-192	4	1
α-helix	202-203	2
β-strand	204-208	5	1
α-helix	209-216	8
α-helix	220-231	12
α-helix	243-253	11
α-helix	256-260	5
α-helix	269-271	3
α-helix	276-284	9
α-helix	291-293	3
α-helix	303-307	5
α-helix	308-313	6
α-helix	318-324	7

Chain B: 20 helices, 7 β-strands

Element	Residues	Length	Sheet
α-helix	6-13	8
α-helix	15-17	3
β-strand	18-21	4	2
α-helix	23-26	4
β-strand	30-34	5	2
α-helix	35-44	10
α-helix	62-76	15
β-strand	80-85	6	2
α-helix	135-148	14
β-strand	152-154	3	2
α-helix	159-168	10
β-strand	174-176	3	2
α-helix	181-184	4
β-strand	189-192	4	2
α-helix	198-200	3
α-helix	202-203	2
β-strand	204-208	5	2
α-helix	209-216	8
α-helix	220-230	11
α-helix	243-253	11
α-helix	256-260	5
α-helix	269-271	3
α-helix	276-284	9
α-helix	291-293	3
α-helix	303-307	5
α-helix	308-313	6
α-helix	318-324	7

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Flap endonuclease 1	A, B	protein	342	Homo sapiens	P39748 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>9RCI_1 Flap endonuclease 1 (chains A, B)
MGIQGLAKLIADVAPSAIRENDIKSYFGRKVAIDASMSIYQFLIAVRQGGDVLQNEEGET
TSHLMGMFYRTIRMMENGIKPVYVFDGKPPQLKSGELAKRSERRAEAEKQLQQAQAAGAE
QEVEKFTKRLVKVTKQHNDECKHLLSLMGIPYLDAPSEAEASCAALVKAGKVYAAATEDM
DCLTFGSPVLMRHLTASEAKKLPIQEFHLSRILQELGLNQEQFVDLCILLGSDYCESIRG
IGPKRAVDLIQKHKSIEEIVRRLDPNKYPVPENWLHKEAHQLFLEPEVLDPESVELKWSE
PNEEELIKFMCGEKQFSEERIRSGVKRLSKSRQGSTLEVLFQ

Ligands and cofactors

ID	Name	Formula	Copies
MG	Magnesium ion	Mg	4
A1JD4	(3~{S})-13-[(1~{S})-1-(2-methylquinolin-7-yl)ethoxy]-11-oxidanyl-5-oxa-1,8-diaz…	C23 H23 N3 O5	2

Water and common crystallization additives (EDO) are not listed.

Primary citation

Fragment-Based Discovery and Structure-Led Optimization of MSC778, the First Potent, Selective, and Orally Bioavailable FEN1 Inhibitor. Mann, S.E., Lefranc, J., Alkhatib, O. et al. J Med Chem (2025) 68:20410-20434. DOI 10.1021/acs.jmedchem.5c01526 · PubMed

Other PDB entries of the same protein (UniProt P39748 (AlphaFold model), which also has an AlphaFold model), best resolution first:

1U7B 1.88 Å, Crystal structure of hPCNA bound to residues 331-350 of the flap endonuclease-1 (FEN1)
5ZOD 1.9 Å, Crystal Structure of hFen1 in apo form
5ZOE 1.95 Å, Crystal Structure of D181A hFen1 in complex with DNA
5E0V 2.07 Å, Human PCNA variant (S228I) complexed with FEN1 at 2.1 Angstroms
5K97 2.1 Å, Flap endonuclease 1 (FEN1) D233N with cleaved product fragment and Sm3+
5KSE 2.1 Å, Flap endonuclease 1 (FEN1) R100A with 5'-flap substrate DNA and Sm3+
9RDI 2.1 Å, Crystal Structure of Flap Endonuclease FEN1 with Compound 5
3Q8K 2.2 Å, Crystal Structure of Human Flap Endonuclease FEN1 (WT) in complex with product 5'-flap…
5ZOF 2.25 Å, Crystal Structure of D181A/R192F hFen1 in complex with DNA
5ZOG 2.3 Å, Crystal Structure of R192F hFen1 in complex with DNA
3Q8L 2.32 Å, Crystal Structure of Human Flap Endonuclease FEN1 (WT) in complex with substrate 5'-flap…
3UVU 2.38 Å, Structural basis of nuclear import of Flap endonuclease 1 (FEN1)

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