Chlorine 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:

Fluorine

(F)

2 atoms

The binding sites of Chlorine 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 Chlorine atom.
In total 2 binding sites of Chlorine 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 Chlorine binding site number: 1; 2;

Chlorine 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 Chlorine with other atoms in the Cl 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:Cl701 b:41.3 occ:1.00 CL1 A:EA6701 0.0 41.3 1.0 C14 A:EA6701 1.7 35.2 1.0 C13 A:EA6701 2.6 35.4 1.0 C9 A:EA6701 2.7 33.4 1.0 O2 A:EA6701 2.9 35.2 1.0 O A:HOH1136 3.7 53.7 1.0 CD2 A:LEU119 3.8 37.1 1.0 C12 A:EA6701 3.9 36.4 1.0 C10 A:EA6701 4.0 33.6 1.0 SD A:MET55 4.1 63.0 1.0 CG2 A:ILE112 4.2 34.1 1.0 CE2 A:PHE58 4.2 35.9 1.0 C8 A:EA6701 4.3 36.6 1.0 CB A:PHE116 4.4 42.0 1.0 CG A:PHE116 4.4 44.3 1.0 C11 A:EA6701 4.5 34.5 1.0 CD1 A:PHE116 4.5 55.0 1.0 O A:HOH977 4.5 30.4 1.0 O A:HOH1095 4.6 40.0 1.0 CG1 A:ILE112 4.7 33.7 1.0 CD2 A:PHE58 4.8 35.0 1.0 CD1 A:ILE112 4.8 35.4 1.0 C7 A:EA6701 4.8 34.6 1.0 F1 A:EA6701 5.0 38.1 1.0 CZ A:PHE58 5.0 39.2 1.0

Chlorine 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 Chlorine with other atoms in the Cl 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:Cl701 b:64.4 occ:1.00 CL1 B:EA6701 0.0 64.4 1.0 C14 B:EA6701 1.7 47.2 1.0 C9 B:EA6701 2.7 49.8 1.0 C13 B:EA6701 2.7 48.2 1.0 O2 B:EA6701 2.8 51.9 1.0 C12 B:EA6701 3.9 54.0 1.0 C10 B:EA6701 4.0 51.6 1.0 CD2 B:LEU119 4.1 86.9 1.0 CE2 B:PHE58 4.1 67.6 1.0 C8 B:EA6701 4.2 59.5 1.0 CG2 B:ILE112 4.2 63.3 1.0 SD B:MET55 4.3 76.5 1.0 O B:HOH992 4.3 41.7 1.0 C11 B:EA6701 4.5 49.7 1.0 CG B:PHE116 4.5 99.0 1.0 CB B:PHE116 4.6 99.0 1.0 CE B:MET55 4.6 79.3 1.0 CD1 B:ILE112 4.6 68.2 1.0 CD2 B:PHE58 4.7 66.8 1.0 C7 B:EA6701 4.7 53.8 1.0 CD2 B:PHE116 4.8 99.0 1.0 O B:HOH1110 4.8 68.6 1.0 CD1 B:PHE116 4.8 99.0 1.0 CZ B:PHE58 4.9 73.8 1.0 CG1 B:ILE112 5.0 66.0 1.0 F1 B:EA6701 5.0 57.8 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