Fluorine in PDB 7mxn: PRMT5(M420T Mutant):MEP50 Complexed with Inhibitor Pf-06939999

All present enzymatic activity of PRMT5(M420T Mutant):MEP50 Complexed with Inhibitor Pf-06939999:
2.1.1.320;

The structure of PRMT5(M420T Mutant):MEP50 Complexed with Inhibitor Pf-06939999, PDB code: 7mxn 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)	109.19 / 2.55
Space group	I 2 2 2
Cell size a, b, c (Å), α, β, γ (°)	100.769, 137.811, 178.947, 90, 90, 90
R / Rfree (%)	23.6 / 27.7

The binding sites of Fluorine atom in the PRMT5(M420T Mutant):MEP50 Complexed with Inhibitor Pf-06939999 (pdb code 7mxn). 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(M420T Mutant):MEP50 Complexed with Inhibitor Pf-06939999, PDB code: 7mxn:
Jump to Fluorine binding site number: 1; 2; 3;

Fluorine binding site 1 out of 3 in the PRMT5(M420T Mutant):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(M420T Mutant):MEP50 Complexed with Inhibitor Pf-06939999 within 5.0Å range: probe atom residue distance (Å) B Occ A:F701 b:67.9 occ:1.00 F3 A:ZR1701 0.0 67.9 1.0 C16 A:ZR1701 1.3 67.1 1.0 C17 A:ZR1701 2.3 67.8 1.0 C15 A:ZR1701 2.4 65.6 1.0 F1 A:ZR1701 2.6 71.4 1.0 C21 A:ZR1701 2.8 64.5 1.0 C22 A:ZR1701 2.8 70.3 1.0 CB A:PHE327 3.0 71.7 1.0 OE2 A:GLU435 3.0 80.1 1.0 CG A:PHE327 3.1 72.9 1.0 OH A:TYR334 3.4 83.6 1.0 CD A:GLU435 3.4 76.9 1.0 OE1 A:GLU435 3.4 75.2 1.0 CD2 A:PHE327 3.5 73.8 1.0 NZ A:LYS333 3.5 90.1 1.0 C18 A:ZR1701 3.6 66.1 1.0 C14 A:ZR1701 3.6 64.8 1.0 CD1 A:PHE327 3.8 74.1 1.0 O A:PHE327 4.0 74.3 1.0 C13 A:ZR1701 4.1 64.7 1.0 CA A:PHE327 4.1 71.8 1.0 F2 A:ZR1701 4.1 71.4 1.0 C20 A:ZR1701 4.3 63.8 1.0 C A:PHE327 4.3 73.8 1.0 CE2 A:PHE327 4.3 74.6 1.0 CG A:GLU435 4.6 71.1 1.0 CE1 A:PHE327 4.6 74.7 1.0 CZ A:TYR334 4.7 81.5 1.0 OG A:SER578 4.8 81.6 1.0 CZ A:PHE327 4.8 74.5 1.0 CE A:LYS333 4.8 89.3 1.0 C19 A:ZR1701 4.9 63.9 1.0

Fluorine binding site 2 out of 3 in the PRMT5(M420T Mutant):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(M420T Mutant):MEP50 Complexed with Inhibitor Pf-06939999 within 5.0Å range: probe atom residue distance (Å) B Occ A:F701 b:71.4 occ:1.00 F1 A:ZR1701 0.0 71.4 1.0 C22 A:ZR1701 1.4 70.3 1.0 F2 A:ZR1701 2.2 71.4 1.0 C17 A:ZR1701 2.4 67.8 1.0 F3 A:ZR1701 2.6 67.9 1.0 C16 A:ZR1701 2.9 67.1 1.0 CB A:PHE327 3.2 71.7 1.0 OH A:TYR334 3.3 83.6 1.0 C18 A:ZR1701 3.6 66.1 1.0 CG A:PRO370 3.7 80.7 1.0 CG A:PHE327 4.0 72.9 1.0 O A:TYR324 4.1 62.6 1.0 CD2 A:PHE327 4.1 73.8 1.0 C A:PHE327 4.1 73.8 1.0 CD1 A:TYR324 4.1 57.2 1.0 O A:PHE327 4.2 74.3 1.0 C15 A:ZR1701 4.2 65.6 1.0 CA A:PHE327 4.3 71.8 1.0 OE2 A:GLU328 4.3 88.7 1.0 OE1 A:GLU435 4.3 75.2 1.0 N A:GLU328 4.4 74.8 1.0 CD A:PRO370 4.4 78.8 1.0 CG A:GLU328 4.5 81.2 1.0 CA A:TYR324 4.6 61.2 1.0 CZ A:TYR334 4.7 81.5 1.0 C13 A:ZR1701 4.7 64.7 1.0 C A:TYR324 4.8 62.6 1.0 CD A:GLU328 4.9 85.9 1.0 CB A:PRO370 4.9 80.1 1.0 CA A:GLU328 4.9 75.4 1.0 CE1 A:TYR324 4.9 57.1 1.0 OE2 A:GLU435 4.9 80.1 1.0 CB A:TYR324 4.9 59.2 1.0 CD A:GLU435 5.0 76.9 1.0

Fluorine binding site 3 out of 3 in the PRMT5(M420T Mutant):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(M420T Mutant):MEP50 Complexed with Inhibitor Pf-06939999 within 5.0Å range: probe atom residue distance (Å) B Occ A:F701 b:71.4 occ:1.00 F2 A:ZR1701 0.0 71.4 1.0 C22 A:ZR1701 1.4 70.3 1.0 F1 A:ZR1701 2.2 71.4 1.0 C17 A:ZR1701 2.5 67.8 1.0 C18 A:ZR1701 2.9 66.1 1.0 CA A:GLY367 3.4 67.4 1.0 CD1 A:TYR324 3.5 57.2 1.0 CD A:PRO370 3.7 78.8 1.0 CG A:PRO370 3.7 80.7 1.0 C16 A:ZR1701 3.7 67.1 1.0 CE1 A:TYR324 3.8 57.1 1.0 O A:ALA366 3.9 67.2 1.0 N A:ARG368 4.0 68.0 1.0 N A:GLY367 4.1 67.4 1.0 F3 A:ZR1701 4.1 67.9 1.0 C A:ALA366 4.2 67.5 1.0 C A:GLY367 4.2 67.5 1.0 C13 A:ZR1701 4.3 64.7 1.0 OE2 A:GLU328 4.5 88.7 1.0 CG A:TYR324 4.6 57.6 1.0 OH A:TYR334 4.7 83.6 1.0 OE1 A:GLU435 4.7 75.2 1.0 C15 A:ZR1701 4.9 65.6 1.0 O2 A:ZR1701 5.0 61.2 1.0 CB A:TYR324 5.0 59.2 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