Fluorine in PDB 8e23: Human Dna Polymerase Theta in Complex with Allosteric Inhibitor

All present enzymatic activity of Human Dna Polymerase Theta in Complex with Allosteric Inhibitor:
2.7.7.7;

The structure of Human Dna Polymerase Theta in Complex with Allosteric Inhibitor, PDB code: 8e23 was solved by P.Mader, V.P.T.Pau, F.Sicheri, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	73.53 / 2.59
Space group	C 1 2 1
Cell size a, b, c (Å), α, β, γ (°)	246.85, 69.32, 147.43, 90, 122.55, 90
R / Rfree (%)	24.7 / 29.5

The structure of Human Dna Polymerase Theta in Complex with Allosteric Inhibitor also contains other interesting chemical elements:

Magnesium

(Mg)

2 atoms

The binding sites of Fluorine atom in the Human Dna Polymerase Theta in Complex with Allosteric Inhibitor (pdb code 8e23). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 3 binding sites of Fluorine where determined in the Human Dna Polymerase Theta in Complex with Allosteric Inhibitor, PDB code: 8e23:
Jump to Fluorine binding site number: 1; 2; 3;

Fluorine binding site 1 out of 3 in the Human Dna Polymerase Theta in Complex with Allosteric Inhibitor


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Human Dna Polymerase Theta in Complex with Allosteric Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ A:F2602 b:74.8 occ:1.00 F15 A:UAF2602 0.0 74.8 1.0 C14 A:UAF2602 1.3 66.6 1.0 F17 A:UAF2602 2.1 72.1 1.0 F16 A:UAF2602 2.1 68.8 1.0 C13 A:UAF2602 2.4 58.7 1.0 C03 A:UAF2602 3.1 69.9 1.0 N06 A:UAF2602 3.1 72.7 1.0 CD1 A:PHE2416 3.2 65.9 1.0 C05 A:UAF2602 3.3 71.9 1.0 S04 A:UAF2602 3.4 82.3 1.0 CB A:PHE2416 3.5 82.6 1.0 CG A:PHE2416 3.5 67.5 1.0 N02 A:UAF2602 3.6 81.6 1.0 C12 A:UAF2602 3.6 63.4 1.0 CD1 A:ILE2389 3.8 59.4 1.0 C19 A:UAF2602 3.9 78.5 1.0 CE1 A:PHE2416 4.0 78.4 1.0 C18 A:UAF2602 4.1 72.7 1.0 CG2 A:ILE2389 4.1 58.4 1.0 N07 A:UAF2602 4.3 74.3 1.0 CB A:ILE2389 4.4 67.0 1.0 C01 A:UAF2602 4.4 68.2 1.0 CA A:PHE2416 4.6 72.1 1.0 C08 A:UAF2602 4.6 70.6 1.0 CD2 A:PHE2416 4.6 74.0 1.0 C11 A:UAF2602 4.6 61.9 1.0 CG1 A:ILE2389 4.7 64.1 1.0 C20 A:UAF2602 4.9 72.7 1.0 CZ A:PHE2416 5.0 72.2 1.0 O A:TYR2412 5.0 89.9 1.0

Fluorine binding site 2 out of 3 in the Human Dna Polymerase Theta in Complex with Allosteric Inhibitor


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Human Dna Polymerase Theta in Complex with Allosteric Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ A:F2602 b:68.8 occ:1.00 F16 A:UAF2602 0.0 68.8 1.0 C14 A:UAF2602 1.3 66.6 1.0 F15 A:UAF2602 2.1 74.8 1.0 F17 A:UAF2602 2.1 72.1 1.0 C13 A:UAF2602 2.4 58.7 1.0 C12 A:UAF2602 2.9 63.4 1.0 C11 A:UAF2602 3.3 61.9 1.0 CD1 A:PHE2416 3.4 65.9 1.0 CE1 A:PHE2416 3.5 78.4 1.0 O A:CYS2386 3.6 62.0 1.0 N06 A:UAF2602 3.7 72.7 1.0 CB A:ILE2389 3.7 67.0 1.0 CG2 A:ILE2389 3.9 58.4 1.0 CA A:CYS2386 3.9 55.0 1.0 CG1 A:ILE2390 4.1 62.4 1.0 CG A:PHE2416 4.1 67.5 1.0 C A:CYS2386 4.2 53.9 1.0 CZ A:PHE2416 4.2 72.2 1.0 CD1 A:ILE2389 4.2 59.4 1.0 C08 A:UAF2602 4.3 70.6 1.0 SG A:CYS2386 4.3 68.0 1.0 CG1 A:ILE2389 4.5 64.1 1.0 C05 A:UAF2602 4.5 71.9 1.0 CB A:CYS2386 4.6 56.7 1.0 N A:ILE2390 4.6 62.0 1.0 O A:ILE2385 4.6 55.3 1.0 N07 A:UAF2602 4.6 74.3 1.0 CD1 A:ILE2390 4.7 55.3 1.0 CD2 A:PHE2416 4.7 74.0 1.0 CB A:PHE2416 4.8 82.6 1.0 CE2 A:PHE2416 4.8 83.7 1.0 CA A:ILE2389 4.8 72.7 1.0 C10 A:UAF2602 4.8 64.6 1.0 C03 A:UAF2602 4.9 69.9 1.0 CD1 A:ILE2362 4.9 62.6 1.0 C A:ILE2389 4.9 67.1 1.0 N A:CYS2386 5.0 57.8 1.0

Fluorine binding site 3 out of 3 in the Human Dna Polymerase Theta in Complex with Allosteric Inhibitor


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Human Dna Polymerase Theta in Complex with Allosteric Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ A:F2602 b:72.1 occ:1.00 F17 A:UAF2602 0.0 72.1 1.0 C14 A:UAF2602 1.4 66.6 1.0 F15 A:UAF2602 2.1 74.8 1.0 F16 A:UAF2602 2.1 68.8 1.0 C13 A:UAF2602 2.4 58.7 1.0 N06 A:UAF2602 3.2 72.7 1.0 C05 A:UAF2602 3.4 71.9 1.0 CD1 A:ILE2362 3.6 62.6 1.0 C12 A:UAF2602 3.6 63.4 1.0 CA A:CYS2386 3.7 55.0 1.0 CD1 A:ILE2389 3.8 59.4 1.0 C19 A:UAF2602 3.9 78.5 1.0 C03 A:UAF2602 4.0 69.9 1.0 CB A:CYS2386 4.2 56.7 1.0 C18 A:UAF2602 4.3 72.7 1.0 N A:CYS2386 4.3 57.8 1.0 O A:ILE2385 4.3 55.3 1.0 N07 A:UAF2602 4.4 74.3 1.0 N02 A:UAF2602 4.4 81.6 1.0 C20 A:UAF2602 4.4 72.7 1.0 CG2 A:ILE2362 4.5 78.4 1.0 CG1 A:ILE2362 4.5 63.8 1.0 CB A:ILE2389 4.5 67.0 1.0 C A:ILE2385 4.5 56.5 1.0 O A:CYS2386 4.5 62.0 1.0 C11 A:UAF2602 4.5 61.9 1.0 CG1 A:ILE2389 4.6 64.1 1.0 C08 A:UAF2602 4.6 70.6 1.0 CG2 A:ILE2385 4.6 60.4 1.0 SG A:CYS2386 4.6 68.0 1.0 C A:CYS2386 4.6 53.9 1.0 S04 A:UAF2602 4.8 82.3 1.0 CG2 A:ILE2389 4.9 58.4 1.0 CD1 A:PHE2416 4.9 65.9 1.0

M.Bubenik, P.Mader, P.Mochirian, F.Vallee, J.Clark, J.F.Truchon, A.L.Perryman, V.Pau, I.Kurinov, K.E.Zahn, M.E.Leclaire, R.Papp, M.C.Mathieu, M.Hamel, N.M.Duffy, C.Godbout, M.Casas-Selves, J.P.Falgueyret, P.S.Baruah, O.Nicolas, R.Stocco, H.Poirier, G.Martino, A.B.Fortin, A.Roulston, A.Chefson, S.Dorich, M.St-Onge, P.Patel, C.Pellerin, S.Ciblat, T.Pinter, F.Barabe, M.El Bakkouri, P.Parikh, C.Gervais, A.Sfeir, Y.Mamane, S.J.Morris, W.C.Black, F.Sicheri, M.Gallant. Identification of Rp-6685 , An Orally Bioavailable Compound That Inhibits the Dna Polymerase Activity of Pol Theta. J.Med.Chem. V. 65 13198 2022.
ISSN: ISSN 0022-2623
PubMed: 36126059
DOI: 10.1021/ACS.JMEDCHEM.2C00998