Fluorine in PDB 6cdj: Hiv-1 Wild Type Protease with Grl-03314A, 6-5-5-Ring Fused Umbrella- Like Tetrahydropyranofuran As the P2-Ligand, A Cyclopropylaminobenzothiazole As the P2'-Ligand and 3,5- Difluorophenylmethyl As the P1-Ligand

The structure of Hiv-1 Wild Type Protease with Grl-03314A, 6-5-5-Ring Fused Umbrella- Like Tetrahydropyranofuran As the P2-Ligand, A Cyclopropylaminobenzothiazole As the P2'-Ligand and 3,5- Difluorophenylmethyl As the P1-Ligand, PDB code: 6cdj was solved by Y.-F.Wang, J.Agniswamy, I.T.Weber, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	50.00 / 1.13
Space group	P 21 21 2
Cell size a, b, c (Å), α, β, γ (°)	58.959, 86.077, 46.157, 90.00, 90.00, 90.00
R / Rfree (%)	14.3 / 17.3

The structure of Hiv-1 Wild Type Protease with Grl-03314A, 6-5-5-Ring Fused Umbrella- Like Tetrahydropyranofuran As the P2-Ligand, A Cyclopropylaminobenzothiazole As the P2'-Ligand and 3,5- Difluorophenylmethyl As the P1-Ligand also contains other interesting chemical elements:

Chlorine	(Cl)	3 atoms
Sodium	(Na)	1 atom

The binding sites of Fluorine atom in the Hiv-1 Wild Type Protease with Grl-03314A, 6-5-5-Ring Fused Umbrella- Like Tetrahydropyranofuran As the P2-Ligand, A Cyclopropylaminobenzothiazole As the P2'-Ligand and 3,5- Difluorophenylmethyl As the P1-Ligand (pdb code 6cdj). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 4 binding sites of Fluorine where determined in the Hiv-1 Wild Type Protease with Grl-03314A, 6-5-5-Ring Fused Umbrella- Like Tetrahydropyranofuran As the P2-Ligand, A Cyclopropylaminobenzothiazole As the P2'-Ligand and 3,5- Difluorophenylmethyl As the P1-Ligand, PDB code: 6cdj:
Jump to Fluorine binding site number: 1; 2; 3; 4;

Fluorine binding site 1 out of 4 in the Hiv-1 Wild Type Protease with Grl-03314A, 6-5-5-Ring Fused Umbrella- Like Tetrahydropyranofuran As the P2-Ligand, A Cyclopropylaminobenzothiazole As the P2'-Ligand and 3,5- Difluorophenylmethyl As the P1-Ligand


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Hiv-1 Wild Type Protease with Grl-03314A, 6-5-5-Ring Fused Umbrella- Like Tetrahydropyranofuran As the P2-Ligand, A Cyclopropylaminobenzothiazole As the P2'-Ligand and 3,5- Difluorophenylmethyl As the P1-Ligand within 5.0Å range: probe atom residue distance (Å) B Occ A:F201 b:16.5 occ:0.55 F61 A:GR8201 0.0 16.5 0.6 C34 A:GR8201 1.4 12.9 0.6 C35 A:GR8201 2.3 13.0 0.6 C33 A:GR8201 2.4 10.9 0.6 O B:HOH285 2.6 18.5 0.5 C15 A:GR8201 3.0 13.9 0.5 O3 A:GOL204 3.4 31.0 0.5 C29 A:GR8201 3.4 12.6 0.6 O1 A:GOL204 3.5 29.2 0.5 CG2 B:VAL82 3.6 29.3 0.5 C36 A:GR8201 3.6 12.4 0.6 NH2 B:ARG8 3.6 18.0 0.6 C38 A:GR8201 3.7 9.2 0.6 NH1 B:ARG8 3.7 21.0 0.6 CZ B:ARG8 3.8 18.0 0.6 CG1 B:VAL82 3.8 28.5 0.6 O A:HOH350 3.9 15.8 0.5 O A:HOH344 3.9 16.8 1.0 CG2 B:VAL82 4.0 21.1 0.6 C30 A:GR8201 4.0 12.8 0.6 C3 A:GOL204 4.1 27.2 0.5 C37 A:GR8201 4.1 10.7 0.6 C31 A:GR8201 4.1 11.7 0.6 CB B:VAL82 4.3 20.9 0.5 C13 A:GR8201 4.3 9.2 0.5 C12 A:GR8201 4.4 10.6 0.5 C1 A:GOL204 4.4 32.6 0.5 CB B:VAL82 4.6 18.4 0.6 C2 A:GOL204 4.6 32.7 0.5 F62 A:GR8201 4.7 14.9 0.6 O28 A:GR8201 4.7 11.0 0.6 CG1 B:VAL82 4.7 19.5 0.5 NE B:ARG8 4.7 20.0 0.6 CD2 B:LEU23 4.8 15.2 1.0 O A:GLY27 4.8 10.4 1.0 C32 A:GR8201 4.9 9.7 0.6

Fluorine binding site 2 out of 4 in the Hiv-1 Wild Type Protease with Grl-03314A, 6-5-5-Ring Fused Umbrella- Like Tetrahydropyranofuran As the P2-Ligand, A Cyclopropylaminobenzothiazole As the P2'-Ligand and 3,5- Difluorophenylmethyl As the P1-Ligand


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Hiv-1 Wild Type Protease with Grl-03314A, 6-5-5-Ring Fused Umbrella- Like Tetrahydropyranofuran As the P2-Ligand, A Cyclopropylaminobenzothiazole As the P2'-Ligand and 3,5- Difluorophenylmethyl As the P1-Ligand within 5.0Å range: probe atom residue distance (Å) B Occ A:F201 b:16.8 occ:0.45 F61 A:GR8201 0.0 16.8 0.5 C34 A:GR8201 1.4 12.6 0.5 O B:HOH231 2.4 23.0 0.6 C35 A:GR8201 2.4 12.4 0.5 C33 A:GR8201 2.4 11.2 0.5 O A:HOH388 2.7 18.4 0.5 C15 A:GR8201 3.2 16.5 0.6 CG2 A:VAL82 3.2 31.0 1.0 C29 A:GR8201 3.4 12.7 0.5 NH1 A:ARG8 3.5 22.0 0.6 NH2 A:ARG8 3.6 24.9 0.6 C36 A:GR8201 3.6 10.9 0.5 C38 A:GR8201 3.6 9.2 0.5 CZ A:ARG8 3.7 24.0 0.6 O A:HOH386 3.9 31.8 0.6 O B:HOH245 3.9 15.1 0.6 C31 A:GR8201 4.0 13.2 0.5 C30 A:GR8201 4.0 14.0 0.5 O B:HOH241 4.1 16.1 1.0 C37 A:GR8201 4.1 10.4 0.5 CB A:VAL82 4.2 22.7 1.0 C12 A:GR8201 4.3 12.6 0.6 C13 A:GR8201 4.4 12.9 0.6 CG1 A:VAL82 4.6 26.6 1.0 NE A:ARG8 4.6 21.5 0.6 O28 A:GR8201 4.7 12.2 0.5 F62 A:GR8201 4.7 13.9 0.5 O B:GLY48 4.8 15.4 0.6 C32 A:GR8201 4.9 10.2 0.5 O B:GLY27 4.9 11.7 1.0 CD2 A:LEU23 5.0 17.0 1.0 CZ A:ARG8 5.0 21.6 0.5

Fluorine binding site 3 out of 4 in the Hiv-1 Wild Type Protease with Grl-03314A, 6-5-5-Ring Fused Umbrella- Like Tetrahydropyranofuran As the P2-Ligand, A Cyclopropylaminobenzothiazole As the P2'-Ligand and 3,5- Difluorophenylmethyl As the P1-Ligand


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Hiv-1 Wild Type Protease with Grl-03314A, 6-5-5-Ring Fused Umbrella- Like Tetrahydropyranofuran As the P2-Ligand, A Cyclopropylaminobenzothiazole As the P2'-Ligand and 3,5- Difluorophenylmethyl As the P1-Ligand within 5.0Å range: probe atom residue distance (Å) B Occ A:F201 b:14.9 occ:0.55 F62 A:GR8201 0.0 14.9 0.6 C36 A:GR8201 1.4 12.4 0.6 CG B:PRO81 2.0 23.0 0.5 C35 A:GR8201 2.3 13.0 0.6 C37 A:GR8201 2.4 10.7 0.6 CD B:PRO81 2.9 24.2 0.6 CA A:GLY49 2.9 21.3 0.6 CD B:PRO81 2.9 24.1 0.5 C A:GLY49 3.0 17.8 0.6 CG B:PRO81 3.0 24.1 0.6 N A:ILE50 3.0 14.9 0.6 C14 A:GR8201 3.1 11.4 0.5 CA A:GLY49 3.2 19.6 0.5 C A:GLY49 3.2 13.4 0.5 CB B:PRO81 3.3 21.9 0.5 N A:ILE50 3.4 14.4 0.5 C34 A:GR8201 3.6 12.9 0.6 CB B:PRO81 3.6 21.7 0.6 C38 A:GR8201 3.6 9.2 0.6 CA A:ILE50 3.7 14.9 0.5 O A:GLY49 3.7 16.7 0.6 O A:GLY49 3.8 17.2 0.5 C15 A:GR8201 3.8 13.9 0.5 C13 A:GR8201 3.9 9.2 0.5 CA A:ILE50 4.0 13.6 0.6 CG1 A:ILE50 4.0 21.3 1.0 C33 A:GR8201 4.1 10.9 0.6 N B:PRO81 4.1 21.3 0.5 N B:PRO81 4.1 20.9 0.6 N A:GLY49 4.2 19.4 0.6 N A:GLY49 4.3 17.5 0.5 CA B:PRO81 4.3 22.2 0.5 CB A:ILE50 4.4 17.2 1.0 CA B:PRO81 4.4 22.0 0.6 C12 A:GR8201 4.5 10.6 0.5 O A:GLY48 4.5 32.3 0.6 O A:GLY48 4.6 12.2 0.5 OG1 B:THR80 4.6 16.7 1.0 O22 A:GR8201 4.6 12.4 0.6 F61 A:GR8201 4.7 16.5 0.6 N B:VAL82 4.7 18.1 1.0 O A:HOH302 4.7 16.7 1.0 CG2 B:VAL82 4.7 21.1 0.6 O10 A:GR8201 4.8 11.2 0.5 C B:PRO81 4.8 20.5 0.6 C32 A:GR8201 4.8 9.7 0.6 C3 A:GOL204 4.8 27.2 0.5 C A:GLY48 4.8 17.2 0.6 O9 A:GR8201 4.8 12.2 0.6 C A:GLY48 4.8 15.8 0.5 C A:ILE50 4.9 16.2 0.5 C B:PRO81 5.0 20.3 0.5 CD1 B:ILE84 5.0 13.8 0.6 CD1 A:ILE50 5.0 29.5 1.0

Fluorine binding site 4 out of 4 in the Hiv-1 Wild Type Protease with Grl-03314A, 6-5-5-Ring Fused Umbrella- Like Tetrahydropyranofuran As the P2-Ligand, A Cyclopropylaminobenzothiazole As the P2'-Ligand and 3,5- Difluorophenylmethyl As the P1-Ligand


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 4 of Hiv-1 Wild Type Protease with Grl-03314A, 6-5-5-Ring Fused Umbrella- Like Tetrahydropyranofuran As the P2-Ligand, A Cyclopropylaminobenzothiazole As the P2'-Ligand and 3,5- Difluorophenylmethyl As the P1-Ligand within 5.0Å range: probe atom residue distance (Å) B Occ A:F201 b:13.9 occ:0.45 F62 A:GR8201 0.0 13.9 0.5 C36 A:GR8201 1.3 10.9 0.5 CG A:PRO81 2.2 17.8 0.6 C35 A:GR8201 2.3 12.4 0.5 C37 A:GR8201 2.3 10.4 0.5 CD A:PRO81 2.9 17.8 0.6 N B:ILE50 2.9 16.7 0.5 O B:GLY49 3.0 17.8 0.6 O B:HOH231 3.0 23.0 0.6 C B:GLY49 3.0 17.7 0.6 CD A:PRO81 3.1 15.8 0.5 C B:GLY49 3.1 16.0 0.5 CG A:PRO81 3.1 16.4 0.5 N B:ILE50 3.3 16.2 0.6 CA B:ILE50 3.4 15.5 0.6 CB A:PRO81 3.5 16.7 0.5 C14 A:GR8201 3.5 15.0 0.6 CB A:PRO81 3.6 17.8 0.6 CA B:GLY49 3.6 21.5 0.5 C34 A:GR8201 3.6 12.6 0.5 O B:GLY49 3.6 17.4 0.5 C38 A:GR8201 3.6 9.2 0.5 CA B:ILE50 3.6 16.3 0.5 CA B:GLY49 3.7 19.8 0.6 C15 A:GR8201 3.8 16.5 0.6 O B:GLY48 4.1 21.2 0.5 C33 A:GR8201 4.1 11.2 0.5 N A:PRO81 4.1 15.0 0.6 CB B:ILE50 4.1 18.3 1.0 N A:PRO81 4.2 14.7 0.5 C13 A:GR8201 4.2 12.9 0.6 N B:GLY49 4.2 18.9 0.6 CG1 B:ILE50 4.4 26.6 1.0 O B:GLY48 4.4 15.4 0.6 CA A:PRO81 4.4 15.2 0.5 CA A:PRO81 4.5 16.2 0.6 C B:ILE50 4.5 14.3 0.6 OG1 A:THR80 4.6 14.3 1.0 N B:GLY49 4.6 22.7 0.5 C B:GLY48 4.6 16.5 0.6 C12 A:GR8201 4.6 12.6 0.6 O22 A:GR8201 4.7 10.2 0.5 N A:VAL82 4.7 14.0 1.0 F61 A:GR8201 4.7 16.8 0.5 C B:GLY48 4.8 20.5 0.5 O A:HOH302 4.8 16.7 1.0 CG2 A:VAL82 4.8 31.0 1.0 O9 A:GR8201 4.8 10.6 0.5 C A:PRO81 4.8 14.7 0.5 O B:HOH216 4.9 29.1 1.0 O10 A:GR8201 4.9 12.9 0.6 C32 A:GR8201 4.9 10.2 0.5 O B:ILE50 4.9 16.8 0.6 C A:PRO81 4.9 16.1 0.6 C B:ILE50 5.0 15.0 0.5

A.K.Ghosh, P.R Nyalapatla, S.Kovela, K.V.Rao, M.Brindisi, H.L.Osswald, M.Amano, M.Aoki, J.Agniswamy, Y.F.Wang, I.T.Weber, H.Mitsuya. Design and Synthesis of Highly Potent Hiv-1 Protease Inhibitors Containing Tricyclic Fused Ring Systems As Novel P2 Ligands: Structure-Activity Studies, Biological and X-Ray Structural Analysis. J. Med. Chem. V. 61 4561 2018.
ISSN: ISSN 1520-4804
PubMed: 29763303
DOI: 10.1021/ACS.JMEDCHEM.8B00298