Fluorine in PDB 7mx7: PRMT5:MEP50 Complexed with Inhibitor Pf-06939999

All present enzymatic activity of PRMT5:MEP50 Complexed with Inhibitor Pf-06939999:
2.1.1.320;

The structure of PRMT5:MEP50 Complexed with Inhibitor Pf-06939999, PDB code: 7mx7 was solved by M.Mctigue, Y.L.Deng, W.Liu, A.Brooun, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	89.13 / 2.49
Space group	I 2 2 2
Cell size a, b, c (Å), α, β, γ (°)	101.597, 137.477, 178.263, 90, 90, 90
R / Rfree (%)	22.2 / 27.9

The binding sites of Fluorine atom in the PRMT5:MEP50 Complexed with Inhibitor Pf-06939999 (pdb code 7mx7). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 3 binding sites of Fluorine where determined in the PRMT5:MEP50 Complexed with Inhibitor Pf-06939999, PDB code: 7mx7:
Jump to Fluorine binding site number: 1; 2; 3;

Fluorine binding site 1 out of 3 in the PRMT5:MEP50 Complexed with Inhibitor Pf-06939999


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of PRMT5:MEP50 Complexed with Inhibitor Pf-06939999 within 5.0Å range: probe atom residue distance (Å) B Occ A:F701 b:57.7 occ:1.00 F3 A:ZR1701 0.0 57.7 1.0 C16 A:ZR1701 1.3 57.2 1.0 C17 A:ZR1701 2.3 58.5 1.0 C15 A:ZR1701 2.4 55.4 1.0 F1 A:ZR1701 2.6 63.6 1.0 C21 A:ZR1701 2.8 54.2 1.0 C22 A:ZR1701 2.8 62.0 1.0 CB A:PHE327 2.9 62.9 1.0 OE2 A:GLU435 3.1 72.5 1.0 CG A:PHE327 3.1 63.6 1.0 CD2 A:PHE327 3.3 64.4 1.0 OH A:TYR334 3.4 68.9 1.0 CD A:GLU435 3.5 66.5 1.0 OE1 A:GLU435 3.5 64.6 1.0 NZ A:LYS333 3.5 76.2 1.0 C18 A:ZR1701 3.6 56.5 1.0 C14 A:ZR1701 3.6 54.9 1.0 CD1 A:PHE327 3.8 64.8 1.0 F2 A:ZR1701 4.1 63.6 1.0 C13 A:ZR1701 4.1 55.3 1.0 CA A:PHE327 4.2 63.1 1.0 CE2 A:PHE327 4.2 65.2 1.0 C20 A:ZR1701 4.3 53.6 1.0 O A:PHE327 4.3 65.2 1.0 C A:PHE327 4.5 64.9 1.0 CE1 A:PHE327 4.6 65.5 1.0 CZ A:TYR334 4.6 67.8 1.0 CG A:GLU435 4.7 59.8 1.0 CZ A:PHE327 4.8 65.2 1.0 CE A:LYS333 4.9 75.7 1.0 C19 A:ZR1701 4.9 53.9 1.0

Fluorine binding site 2 out of 3 in the PRMT5:MEP50 Complexed with Inhibitor Pf-06939999


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of PRMT5:MEP50 Complexed with Inhibitor Pf-06939999 within 5.0Å range: probe atom residue distance (Å) B Occ A:F701 b:63.6 occ:1.00 F1 A:ZR1701 0.0 63.6 1.0 C22 A:ZR1701 1.4 62.0 1.0 F2 A:ZR1701 2.2 63.6 1.0 C17 A:ZR1701 2.4 58.5 1.0 F3 A:ZR1701 2.6 57.7 1.0 C16 A:ZR1701 2.9 57.2 1.0 OH A:TYR334 3.4 68.9 1.0 CB A:PHE327 3.5 62.9 1.0 CG A:PRO370 3.5 69.5 1.0 C18 A:ZR1701 3.6 56.5 1.0 CD2 A:PHE327 4.1 64.4 1.0 CD1 A:TYR324 4.1 49.4 1.0 CD A:PRO370 4.2 68.0 1.0 CG A:PHE327 4.2 63.6 1.0 C15 A:ZR1701 4.2 55.4 1.0 O A:TYR324 4.3 56.1 1.0 OE1 A:GLU435 4.3 64.6 1.0 OE2 A:GLU328 4.3 76.1 1.0 C A:PHE327 4.5 64.9 1.0 CG A:GLU328 4.6 70.4 1.0 O A:PHE327 4.6 65.2 1.0 N A:GLU328 4.6 65.8 1.0 CA A:PHE327 4.6 63.1 1.0 CZ A:TYR334 4.6 67.8 1.0 CA A:TYR324 4.7 54.3 1.0 C13 A:ZR1701 4.7 55.3 1.0 CB A:PRO370 4.8 69.0 1.0 CE1 A:TYR324 4.9 49.5 1.0 OE2 A:GLU435 4.9 72.5 1.0 CD A:GLU328 4.9 73.0 1.0 CD A:GLU435 5.0 66.5 1.0 CB A:TYR324 5.0 52.1 1.0 C A:TYR324 5.0 56.0 1.0

Fluorine binding site 3 out of 3 in the PRMT5:MEP50 Complexed with Inhibitor Pf-06939999


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of PRMT5:MEP50 Complexed with Inhibitor Pf-06939999 within 5.0Å range: probe atom residue distance (Å) B Occ A:F701 b:63.6 occ:1.00 F2 A:ZR1701 0.0 63.6 1.0 C22 A:ZR1701 1.4 62.0 1.0 F1 A:ZR1701 2.2 63.6 1.0 C17 A:ZR1701 2.4 58.5 1.0 C18 A:ZR1701 2.8 56.5 1.0 CA A:GLY367 3.2 59.4 1.0 CD1 A:TYR324 3.3 49.4 1.0 CE1 A:TYR324 3.6 49.5 1.0 C16 A:ZR1701 3.6 57.2 1.0 N A:GLY367 3.8 59.2 1.0 O A:ALA366 3.8 59.9 1.0 N A:ARG368 3.9 60.0 1.0 CD A:PRO370 3.9 68.0 1.0 C A:ALA366 4.0 59.6 1.0 C A:GLY367 4.0 60.0 1.0 F3 A:ZR1701 4.1 57.7 1.0 CG A:PRO370 4.1 69.5 1.0 C13 A:ZR1701 4.1 55.3 1.0 CG A:TYR324 4.4 50.0 1.0 OE2 A:GLU328 4.7 76.1 1.0 O2 A:ZR1701 4.7 52.1 1.0 C15 A:ZR1701 4.8 55.4 1.0 CZ A:TYR324 4.8 50.1 1.0 CB A:TYR324 4.9 52.1 1.0 OH A:TYR334 5.0 68.9 1.0 OE1 A:GLU435 5.0 64.6 1.0 C14 A:ZR1701 5.0 54.9 1.0

K.Jensen-Pergakes, J.Tatlock, K.A.Maegley, I.J.Mcalpine, M.A.Mctigue, T.Xie, C.P.Dillon, Y.Wang, S.Yamazaki, N.Spiegel, M.Shi, A.Nemeth, N.Miller, E.Hendrickson, H.Lam, J.Sherrill, C.Y.Chung, E.A.Mcmillan, S.K.Bryant, P.Palde, J.Braganza, A.Brooun, Y.L.Deng, V.Goshtasbi, S.E.Kephart, R.A.Kumpf, W.Liu, R.L.Patman, E.Rui, S.Scales, M.Tran-Dube, F.Wang, M.Wythes, T.A.Paul. Sam Competitive PRMT5 Inhibitor Pf-06939999 Demonstrates Antitumor Activity in Splicing Dysregulated Nsclc with Decreased Liability of Drug Resistance. Mol.Cancer Ther. 2021.
ISSN: ESSN 1538-8514
PubMed: 34737197
DOI: 10.1158/1535-7163.MCT-21-0620