Fluorine in PDB 6i4b: Plasmodium Falciparum Dihydroorotate Dehydrogenase (Dhodh) Co- Crystallized with 3-Hydroxy-1-Methyl-5-((3-(Trifluoromethyl)Phenoxy) Methyl)-1H-Pyrazole-4-Carboxylic Acid

The structure of Plasmodium Falciparum Dihydroorotate Dehydrogenase (Dhodh) Co- Crystallized with 3-Hydroxy-1-Methyl-5-((3-(Trifluoromethyl)Phenoxy) Methyl)-1H-Pyrazole-4-Carboxylic Acid, PDB code: 6i4b was solved by P.Goyal, S.Sainas, A.C.Pippione, D.Boschi, S.Al-Kadaraghi, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	48.73 / 1.98
Space group	P 1 21 1
Cell size a, b, c (Å), α, β, γ (°)	50.607, 158.121, 61.753, 90.00, 105.67, 90.00
R / Rfree (%)	19.2 / 22.6

The binding sites of Fluorine atom in the Plasmodium Falciparum Dihydroorotate Dehydrogenase (Dhodh) Co- Crystallized with 3-Hydroxy-1-Methyl-5-((3-(Trifluoromethyl)Phenoxy) Methyl)-1H-Pyrazole-4-Carboxylic Acid (pdb code 6i4b). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 6 binding sites of Fluorine where determined in the Plasmodium Falciparum Dihydroorotate Dehydrogenase (Dhodh) Co- Crystallized with 3-Hydroxy-1-Methyl-5-((3-(Trifluoromethyl)Phenoxy) Methyl)-1H-Pyrazole-4-Carboxylic Acid, PDB code: 6i4b:
Jump to Fluorine binding site number: 1; 2; 3; 4; 5; 6;

Fluorine binding site 1 out of 6 in the Plasmodium Falciparum Dihydroorotate Dehydrogenase (Dhodh) Co- Crystallized with 3-Hydroxy-1-Methyl-5-((3-(Trifluoromethyl)Phenoxy) Methyl)-1H-Pyrazole-4-Carboxylic Acid


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Plasmodium Falciparum Dihydroorotate Dehydrogenase (Dhodh) Co- Crystallized with 3-Hydroxy-1-Methyl-5-((3-(Trifluoromethyl)Phenoxy) Methyl)-1H-Pyrazole-4-Carboxylic Acid within 5.0Å range: probe atom residue distance (Å) B Occ A:F603 b:94.8 occ:1.00 F1 A:E2N603 0.0 94.8 1.0 C12 A:E2N603 1.4 93.2 1.0 F3 A:E2N603 2.2 94.7 1.0 F2 A:E2N603 2.2 92.6 1.0 C11 A:E2N603 2.4 89.8 1.0 C10 A:E2N603 2.7 87.7 1.0 C13 A:E2N603 3.6 87.7 1.0 CD2 A:PHE171 4.0 76.7 1.0 CD1 A:LEU191 4.0 54.6 1.0 C9 A:E2N603 4.1 86.6 1.0 CE2 A:PHE171 4.4 77.7 1.0 SD A:MET536 4.5 67.6 1.0 C7 A:E2N603 4.7 84.7 1.0 CG A:PHE171 4.8 76.1 1.0 CD1 A:TYR168 4.9 62.7 1.0 C8 A:E2N603 4.9 85.9 1.0

Fluorine binding site 2 out of 6 in the Plasmodium Falciparum Dihydroorotate Dehydrogenase (Dhodh) Co- Crystallized with 3-Hydroxy-1-Methyl-5-((3-(Trifluoromethyl)Phenoxy) Methyl)-1H-Pyrazole-4-Carboxylic Acid


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Plasmodium Falciparum Dihydroorotate Dehydrogenase (Dhodh) Co- Crystallized with 3-Hydroxy-1-Methyl-5-((3-(Trifluoromethyl)Phenoxy) Methyl)-1H-Pyrazole-4-Carboxylic Acid within 5.0Å range: probe atom residue distance (Å) B Occ A:F603 b:92.6 occ:1.00 F2 A:E2N603 0.0 92.6 1.0 C12 A:E2N603 1.4 93.2 1.0 F3 A:E2N603 2.2 94.7 1.0 F1 A:E2N603 2.2 94.8 1.0 C11 A:E2N603 2.4 89.8 1.0 C13 A:E2N603 2.7 87.7 1.0 CD2 A:LEU187 3.4 61.6 1.0 C10 A:E2N603 3.6 87.7 1.0 CD1 A:LEU191 3.7 54.6 1.0 CG A:LEU187 3.8 58.3 1.0 C7 A:E2N603 4.1 84.7 1.0 CE2 A:PHE171 4.2 77.7 1.0 N A:PHE188 4.3 44.6 1.0 CD2 A:PHE171 4.4 76.7 1.0 CB A:LEU187 4.4 51.0 1.0 CA A:PHE188 4.4 45.3 1.0 O A:CYS184 4.6 52.6 1.0 C A:LEU187 4.7 50.1 1.0 C9 A:E2N603 4.7 86.6 1.0 CB A:PHE188 4.7 44.8 1.0 C8 A:E2N603 4.9 85.9 1.0 O4 A:E2N603 4.9 79.3 1.0 CG A:LEU191 5.0 54.3 1.0

Fluorine binding site 3 out of 6 in the Plasmodium Falciparum Dihydroorotate Dehydrogenase (Dhodh) Co- Crystallized with 3-Hydroxy-1-Methyl-5-((3-(Trifluoromethyl)Phenoxy) Methyl)-1H-Pyrazole-4-Carboxylic Acid


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Plasmodium Falciparum Dihydroorotate Dehydrogenase (Dhodh) Co- Crystallized with 3-Hydroxy-1-Methyl-5-((3-(Trifluoromethyl)Phenoxy) Methyl)-1H-Pyrazole-4-Carboxylic Acid within 5.0Å range: probe atom residue distance (Å) B Occ A:F603 b:94.7 occ:1.00 F3 A:E2N603 0.0 94.7 1.0 C12 A:E2N603 1.4 93.2 1.0 F2 A:E2N603 2.2 92.6 1.0 F1 A:E2N603 2.2 94.8 1.0 C11 A:E2N603 2.3 89.8 1.0 C13 A:E2N603 3.1 87.7 1.0 CD2 A:PHE171 3.2 76.7 1.0 C10 A:E2N603 3.3 87.7 1.0 CE2 A:PHE171 3.5 77.7 1.0 CG A:PHE171 3.7 76.1 1.0 SG A:CYS175 3.7 69.5 1.0 CZ A:PHE171 4.2 79.3 1.0 CB A:PHE171 4.2 71.8 1.0 CD1 A:PHE171 4.3 79.0 1.0 C7 A:E2N603 4.3 84.7 1.0 O A:PHE171 4.4 60.5 1.0 CD2 A:LEU187 4.4 61.6 1.0 C A:PHE171 4.4 62.6 1.0 C9 A:E2N603 4.5 86.6 1.0 CE1 A:PHE171 4.6 79.7 1.0 N A:LEU172 4.6 59.4 1.0 CA A:LEU172 4.7 56.9 1.0 CB A:CYS175 4.7 64.2 1.0 C8 A:E2N603 4.9 85.9 1.0

Fluorine binding site 4 out of 6 in the Plasmodium Falciparum Dihydroorotate Dehydrogenase (Dhodh) Co- Crystallized with 3-Hydroxy-1-Methyl-5-((3-(Trifluoromethyl)Phenoxy) Methyl)-1H-Pyrazole-4-Carboxylic Acid


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 4 of Plasmodium Falciparum Dihydroorotate Dehydrogenase (Dhodh) Co- Crystallized with 3-Hydroxy-1-Methyl-5-((3-(Trifluoromethyl)Phenoxy) Methyl)-1H-Pyrazole-4-Carboxylic Acid within 5.0Å range: probe atom residue distance (Å) B Occ B:F603 b:87.9 occ:1.00 F1 B:E2N603 0.0 87.9 1.0 C12 B:E2N603 1.4 86.1 1.0 F2 B:E2N603 2.3 85.9 1.0 F3 B:E2N603 2.3 86.5 1.0 C11 B:E2N603 2.4 82.8 1.0 C10 B:E2N603 2.7 80.7 1.0 C13 B:E2N603 3.6 80.6 1.0 CD2 B:PHE171 3.7 67.4 1.0 C9 B:E2N603 4.1 79.5 1.0 CE2 B:PHE171 4.3 67.0 1.0 CD1 B:LEU191 4.5 56.2 1.0 SD B:MET536 4.5 66.5 1.0 CG B:PHE171 4.7 67.8 1.0 C7 B:E2N603 4.7 77.7 1.0 CD1 B:TYR168 4.8 62.0 1.0 O B:HOH789 4.8 55.0 1.0 CB B:PHE171 4.8 65.1 1.0 C8 B:E2N603 4.9 78.5 1.0 O B:TYR168 4.9 56.0 1.0

Fluorine binding site 5 out of 6 in the Plasmodium Falciparum Dihydroorotate Dehydrogenase (Dhodh) Co- Crystallized with 3-Hydroxy-1-Methyl-5-((3-(Trifluoromethyl)Phenoxy) Methyl)-1H-Pyrazole-4-Carboxylic Acid


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 5 of Plasmodium Falciparum Dihydroorotate Dehydrogenase (Dhodh) Co- Crystallized with 3-Hydroxy-1-Methyl-5-((3-(Trifluoromethyl)Phenoxy) Methyl)-1H-Pyrazole-4-Carboxylic Acid within 5.0Å range: probe atom residue distance (Å) B Occ B:F603 b:85.9 occ:1.00 F2 B:E2N603 0.0 85.9 1.0 C12 B:E2N603 1.4 86.1 1.0 F3 B:E2N603 2.2 86.5 1.0 F1 B:E2N603 2.3 87.9 1.0 C11 B:E2N603 2.3 82.8 1.0 C13 B:E2N603 2.9 80.6 1.0 C10 B:E2N603 3.4 80.7 1.0 CD1 B:LEU191 3.5 56.2 1.0 CD2 B:LEU187 3.9 63.8 1.0 CG B:LEU187 4.0 61.8 1.0 CE2 B:PHE171 4.1 67.0 1.0 C7 B:E2N603 4.2 77.7 1.0 CD2 B:PHE171 4.2 67.4 1.0 N B:PHE188 4.5 48.8 1.0 C9 B:E2N603 4.6 79.5 1.0 CA B:PHE188 4.6 50.0 1.0 CB B:LEU187 4.7 57.5 1.0 CG B:LEU191 4.8 57.9 1.0 C8 B:E2N603 4.9 78.5 1.0 C B:LEU187 4.9 51.5 1.0 CB B:PHE188 5.0 48.5 1.0 O B:CYS184 5.0 51.7 1.0

Fluorine binding site 6 out of 6 in the Plasmodium Falciparum Dihydroorotate Dehydrogenase (Dhodh) Co- Crystallized with 3-Hydroxy-1-Methyl-5-((3-(Trifluoromethyl)Phenoxy) Methyl)-1H-Pyrazole-4-Carboxylic Acid


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 6 of Plasmodium Falciparum Dihydroorotate Dehydrogenase (Dhodh) Co- Crystallized with 3-Hydroxy-1-Methyl-5-((3-(Trifluoromethyl)Phenoxy) Methyl)-1H-Pyrazole-4-Carboxylic Acid within 5.0Å range: probe atom residue distance (Å) B Occ B:F603 b:86.5 occ:1.00 F3 B:E2N603 0.0 86.5 1.0 C12 B:E2N603 1.4 86.1 1.0 F2 B:E2N603 2.2 85.9 1.0 F1 B:E2N603 2.3 87.9 1.0 C11 B:E2N603 2.3 82.8 1.0 C13 B:E2N603 2.9 80.6 1.0 CD2 B:PHE171 2.9 67.4 1.0 CE2 B:PHE171 3.2 67.0 1.0 C10 B:E2N603 3.4 80.7 1.0 SG B:CYS175 3.5 75.2 1.0 CG B:PHE171 4.0 67.8 1.0 C7 B:E2N603 4.1 77.7 1.0 O B:PHE171 4.3 65.4 1.0 CZ B:PHE171 4.4 64.9 1.0 CB B:CYS175 4.4 68.8 1.0 C B:PHE171 4.5 63.1 1.0 CB B:PHE171 4.5 65.1 1.0 C9 B:E2N603 4.5 79.5 1.0 CA B:LEU172 4.6 57.9 1.0 CD2 B:LEU187 4.7 63.8 1.0 N B:LEU172 4.7 61.6 1.0 C8 B:E2N603 4.8 78.5 1.0 CD1 B:LEU172 5.0 57.0 1.0 CD1 B:PHE171 5.0 68.7 1.0

A.C.Pippione, S.Sainas, P.Goyal, I.Fritzson, G.C.Cassiano, A.Giraudo, M.Giorgis, T.A.Tavella, R.Bagnati, B.Rolando, R.Caing-Carlsson, F.T.M.Costa, C.H.Andrade, S.Al-Karadaghi, D.Boschi, R.Friemann, M.L.Lolli. Hydroxyazole Scaffold-Based Plasmodium Falciparum Dihydroorotate Dehydrogenase Inhibitors: Synthesis, Biological Evaluation and X-Ray Structural Studies. Eur J Med Chem V. 163 266 2018.
ISSN: ISSN 1768-3254
PubMed: 30529545
DOI: 10.1016/J.EJMECH.2018.11.044