Fluorine in PDB 5a00: Structure of Human PARP1 Catalytic Domain Bound to An Isoindolinone Inhibitor

All present enzymatic activity of Structure of Human PARP1 Catalytic Domain Bound to An Isoindolinone Inhibitor:
2.4.2.30;

The structure of Structure of Human PARP1 Catalytic Domain Bound to An Isoindolinone Inhibitor, PDB code: 5a00 was solved by E.Casale, M.Fasolini, G.Papeo, H.Posteri, D.Borghi, A.A.Busel, F.Caprera, M.Ciomei, A.Cirla, E.Corti, M.Danello, M.Fasolini, E.R.Felder, B.Forte, A.Galvani, A.Isacchi, A.Khvat, M.Y.Krasavin, R.Lupi, P.Orsini, R.Perego, E.Pesenti, D.Pezzetta, S.Rainoldi, F.Riccardisirtori, A.Scolaro, F.Sola, F.Zuccotto, D.Donati, A.Montagnoli, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	30.00 / 2.75
Space group	I 2 2 2
Cell size a, b, c (Å), α, β, γ (°)	49.083, 89.392, 193.187, 90.00, 90.00, 90.00
R / Rfree (%)	20.5 / 28

The binding sites of Fluorine atom in the Structure of Human PARP1 Catalytic Domain Bound to An Isoindolinone Inhibitor (pdb code 5a00). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 3 binding sites of Fluorine where determined in the Structure of Human PARP1 Catalytic Domain Bound to An Isoindolinone Inhibitor, PDB code: 5a00:
Jump to Fluorine binding site number: 1; 2; 3;

Fluorine binding site 1 out of 3 in the Structure of Human PARP1 Catalytic Domain Bound to An Isoindolinone Inhibitor


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Structure of Human PARP1 Catalytic Domain Bound to An Isoindolinone Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ A:F2012 b:80.2 occ:1.00 F26 A:D7N2012 0.0 80.2 1.0 C23 A:D7N2012 1.3 80.1 1.0 F27 A:D7N2012 2.2 79.8 1.0 C22 A:D7N2012 2.3 78.8 1.0 C24 A:D7N2012 2.3 80.5 1.0 CG A:GLN759 3.2 62.4 1.0 CB A:GLN759 3.4 61.2 1.0 O A:THR887 3.5 85.3 1.0 C21 A:D7N2012 3.6 77.6 1.0 C25 A:D7N2012 3.6 79.8 1.0 CA A:GLY888 3.7 78.9 1.0 CA A:GLN759 3.8 63.9 1.0 C20 A:D7N2012 4.0 78.1 1.0 CD A:GLN759 4.1 61.0 1.0 CB A:VAL762 4.2 67.4 1.0 CG2 A:VAL762 4.2 68.7 1.0 C A:GLY888 4.3 76.3 1.0 CG1 A:VAL762 4.4 65.3 1.0 O A:GLN759 4.4 63.4 1.0 C A:THR887 4.4 85.8 1.0 N A:GLY888 4.5 81.2 1.0 C A:GLN759 4.6 64.6 1.0 OE1 A:GLN759 4.7 63.0 1.0 NE2 A:GLN759 4.7 60.8 1.0 N A:TYR889 4.8 75.0 1.0 CE2 A:TYR889 4.8 84.9 1.0 O A:GLY888 4.8 70.6 1.0 CD2 A:TYR889 5.0 80.9 1.0 N A:GLN759 5.0 67.8 1.0 O A:HOH3003 5.0 68.9 1.0

Fluorine binding site 2 out of 3 in the Structure of Human PARP1 Catalytic Domain Bound to An Isoindolinone Inhibitor


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Structure of Human PARP1 Catalytic Domain Bound to An Isoindolinone Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ A:F2012 b:79.8 occ:1.00 F27 A:D7N2012 0.0 79.8 1.0 C23 A:D7N2012 1.4 80.1 1.0 F26 A:D7N2012 2.2 80.2 1.0 C24 A:D7N2012 2.4 80.5 1.0 C22 A:D7N2012 2.4 78.8 1.0 C21 A:D7N2012 2.9 77.6 1.0 C25 A:D7N2012 2.9 79.8 1.0 O A:GLN759 3.4 63.4 1.0 CB A:VAL762 3.4 67.4 1.0 C20 A:D7N2012 3.5 78.1 1.0 CG1 A:VAL762 3.5 65.3 1.0 CG A:GLU763 3.8 84.9 1.0 N A:GLU763 3.9 66.7 1.0 C A:GLN759 4.2 64.6 1.0 CA A:GLN759 4.2 63.9 1.0 CB A:GLN759 4.2 61.2 1.0 OE2 A:GLU763 4.3 98.2 1.0 CG2 A:VAL762 4.3 68.7 1.0 C A:VAL762 4.4 65.0 1.0 CA A:GLU763 4.5 69.5 1.0 CA A:VAL762 4.5 65.6 1.0 CD A:GLU763 4.6 92.2 1.0 CB A:GLU763 4.6 76.0 1.0 CG A:GLN759 4.7 62.4 1.0 N16 A:D7N2012 4.8 77.2 1.0 OD2 A:ASP766 4.9 78.4 1.0 C15 A:D7N2012 5.0 75.1 1.0

Fluorine binding site 3 out of 3 in the Structure of Human PARP1 Catalytic Domain Bound to An Isoindolinone Inhibitor


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Structure of Human PARP1 Catalytic Domain Bound to An Isoindolinone Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ A:F2012 b:68.8 occ:1.00 F5 A:D7N2012 0.0 68.8 1.0 C2 A:D7N2012 1.3 70.4 1.0 C1 A:D7N2012 2.3 70.1 1.0 C3 A:D7N2012 2.3 72.1 1.0 O A:PHE897 2.9 54.7 1.0 CB A:ALA898 3.2 57.5 1.0 C A:PHE897 3.3 54.7 1.0 CB A:GLU988 3.4 59.4 1.0 C8 A:D7N2012 3.5 72.1 1.0 C4 A:D7N2012 3.6 68.9 1.0 CE A:LYS903 3.6 53.8 1.0 CA A:ALA898 3.6 57.2 1.0 N A:ALA898 3.6 54.9 1.0 CD A:LYS903 3.6 53.0 1.0 CG A:LYS903 3.8 53.9 1.0 C7 A:D7N2012 4.0 72.5 1.0 O A:ASN987 4.1 59.1 1.0 CA A:GLU988 4.2 57.7 1.0 OE1 A:GLU988 4.2 54.7 1.0 CA A:PHE897 4.3 55.3 1.0 CD A:GLU988 4.4 60.8 1.0 NZ A:LYS903 4.5 55.6 1.0 N A:PHE897 4.5 55.7 1.0 CG A:GLU988 4.5 60.6 1.0 C6 A:D7N2012 4.7 66.1 1.0 C9 A:D7N2012 4.7 72.4 1.0 O28 A:D7N2012 4.8 63.7 1.0 OG A:SER904 4.8 67.7 1.0 CB A:LYS903 4.9 56.4 1.0 C A:TYR896 4.9 54.5 1.0 CE2 A:TYR907 5.0 72.5 1.0

G.M.E.Papeo, H.Posteri, D.Borghi, A.A.Busel, F.Caprera, E.Casale, M.Ciomei, A.Cirla, E.Corti, M.D'anello, M.Fasolini, B.Forte, A.Galvani, A.Isacchi, A.Khvat, M.Y.Krasavin, R.Lupi, P.Orsini, R.Perego, E.Pesenti, D.Pezzetta, S.Rainoldi, F.Riccardi-Sirtori, A.Scolaro, F.Sola, F.Zuccotto, E.R.Felder, D.Donati, A.Montagnoli. Discovery of 2-[1-(4,4-Difluorocyclohexyl) Piperidin-4-Yl]-6-Fluoro-3-Oxo-2, 3-Dihydro-1H-Isoindole-4-Carboxamide (Nms-P118): A Potent, Orally Available and Highly Selective Parp- 1 Inhibitor For Cancer Therapy. J.Med.Chem. V. 58 6875 2015.
ISSN: ISSN 0022-2623
PubMed: 26222319
DOI: 10.1021/ACS.JMEDCHEM.5B00680