Fluorine in PDB 6lhj: Quadruple Mutant (N51I+C59R+S108N+I164L) Plasmodium Falciparum Dihydrofolate Reductase-Thymidylate Synthase (Pfdhfr-Ts) Complexed with C452 (Compound 16) and Nadph

The structure of Quadruple Mutant (N51I+C59R+S108N+I164L) Plasmodium Falciparum Dihydrofolate Reductase-Thymidylate Synthase (Pfdhfr-Ts) Complexed with C452 (Compound 16) and Nadph, PDB code: 6lhj was solved by J.Vanichtanankul, D.Vitsupakorn, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	10.00 / 2.40
Space group	P 21 21 21
Cell size a, b, c (Å), α, β, γ (°)	57.277, 156.483, 164.449, 90.00, 90.00, 90.00
R / Rfree (%)	17.3 / 20.3

The structure of Quadruple Mutant (N51I+C59R+S108N+I164L) Plasmodium Falciparum Dihydrofolate Reductase-Thymidylate Synthase (Pfdhfr-Ts) Complexed with C452 (Compound 16) and Nadph also contains other interesting chemical elements:

Chlorine

(Cl)

2 atoms

The binding sites of Fluorine atom in the Quadruple Mutant (N51I+C59R+S108N+I164L) Plasmodium Falciparum Dihydrofolate Reductase-Thymidylate Synthase (Pfdhfr-Ts) Complexed with C452 (Compound 16) and Nadph (pdb code 6lhj). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 2 binding sites of Fluorine where determined in the Quadruple Mutant (N51I+C59R+S108N+I164L) Plasmodium Falciparum Dihydrofolate Reductase-Thymidylate Synthase (Pfdhfr-Ts) Complexed with C452 (Compound 16) and Nadph, PDB code: 6lhj:
Jump to Fluorine binding site number: 1; 2;

Fluorine binding site 1 out of 2 in the Quadruple Mutant (N51I+C59R+S108N+I164L) Plasmodium Falciparum Dihydrofolate Reductase-Thymidylate Synthase (Pfdhfr-Ts) Complexed with C452 (Compound 16) and Nadph


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Quadruple Mutant (N51I+C59R+S108N+I164L) Plasmodium Falciparum Dihydrofolate Reductase-Thymidylate Synthase (Pfdhfr-Ts) Complexed with C452 (Compound 16) and Nadph within 5.0Å range: probe atom residue distance (Å) B Occ A:F701 b:38.1 occ:1.00 F1 A:EA6701 0.0 38.1 1.0 C12 A:EA6701 1.4 36.4 1.0 C13 A:EA6701 2.3 35.4 1.0 C11 A:EA6701 2.4 34.5 1.0 O A:HOH1117 3.1 61.9 1.0 CD A:PRO113 3.3 35.5 1.0 C14 A:EA6701 3.6 35.2 1.0 C10 A:EA6701 3.6 33.6 1.0 CG A:PRO113 3.7 36.8 1.0 CE2 A:PHE116 3.9 51.7 1.0 C9 A:EA6701 4.1 33.4 1.0 CD2 A:PHE116 4.2 49.0 1.0 CZ A:PHE116 4.5 52.8 1.0 N A:PRO113 4.7 35.5 1.0 CE A:MET55 4.8 58.1 1.0 O A:HOH1042 4.8 49.8 1.0 O A:HOH818 4.8 47.5 1.0 CB A:PRO113 4.9 38.3 1.0 SD A:MET55 4.9 63.0 1.0 CL1 A:EA6701 5.0 41.3 1.0

Fluorine binding site 2 out of 2 in the Quadruple Mutant (N51I+C59R+S108N+I164L) Plasmodium Falciparum Dihydrofolate Reductase-Thymidylate Synthase (Pfdhfr-Ts) Complexed with C452 (Compound 16) and Nadph


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Quadruple Mutant (N51I+C59R+S108N+I164L) Plasmodium Falciparum Dihydrofolate Reductase-Thymidylate Synthase (Pfdhfr-Ts) Complexed with C452 (Compound 16) and Nadph within 5.0Å range: probe atom residue distance (Å) B Occ B:F701 b:57.8 occ:1.00 F1 B:EA6701 0.0 57.8 1.0 C12 B:EA6701 1.4 54.0 1.0 C13 B:EA6701 2.3 48.2 1.0 C11 B:EA6701 2.4 49.7 1.0 CD B:PRO113 3.4 91.1 1.0 CE2 B:PHE116 3.4 96.0 1.0 C14 B:EA6701 3.6 47.2 1.0 CG B:PRO113 3.6 97.3 1.0 C10 B:EA6701 3.6 51.6 1.0 CD2 B:PHE116 4.0 99.0 1.0 C9 B:EA6701 4.1 49.8 1.0 CZ B:PHE116 4.1 99.0 1.0 CE B:MET55 4.4 79.3 1.0 CB B:PRO113 4.7 99.0 1.0 N B:PRO113 4.8 92.3 1.0 SD B:MET55 5.0 76.5 1.0 CL1 B:EA6701 5.0 64.4 1.0

S.Kamchonwongpaisan, N.Charoensetakul, C.Srisuwannaket, S.Taweechai, R.Rattanajak, J.Vanichtanankul, D.Vitsupakorn, U.Arwon, C.Thongpanchang, B.Tarnchompoo, T.Vilaivan, Y.Yuthavong. Flexible Diaminodihydrotriazine Inhibitors of Plasmodium Falciparum Dihydrofolate Reductase: Binding Strengths, Modes of Binding and Their Antimalarial Activities. Eur.J.Med.Chem. V. 195 12263 2020.
ISSN: ISSN 0223-5234
PubMed: 32294614
DOI: 10.1016/J.EJMECH.2020.112263