Fluorine in PDB 6pfh: Crystal Structure of Ts-Dhfr From Cryptosporidium Hominis in Complex with Nadph, Fdump and 2-(2-(4-((2-Amino-4-Oxo-4,7-Dihydro-3H- Pyrrolo[2,3-D]Pyrimidin-5-Yl)Methyl)Benzamido)-4-Cyanophenyl)Acetic Acid.

The structure of Crystal Structure of Ts-Dhfr From Cryptosporidium Hominis in Complex with Nadph, Fdump and 2-(2-(4-((2-Amino-4-Oxo-4,7-Dihydro-3H- Pyrrolo[2,3-D]Pyrimidin-5-Yl)Methyl)Benzamido)-4-Cyanophenyl)Acetic Acid., PDB code: 6pfh was solved by D.C.Czyzyk, M.Valhondo, W.L.Jorgensen, K.S.Anderson, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	29.72 / 2.94
Space group	C 1 2 1
Cell size a, b, c (Å), α, β, γ (°)	214.110, 116.936, 221.376, 90.00, 95.43, 90.00
R / Rfree (%)	18.8 / 21.9

The binding sites of Fluorine atom in the Crystal Structure of Ts-Dhfr From Cryptosporidium Hominis in Complex with Nadph, Fdump and 2-(2-(4-((2-Amino-4-Oxo-4,7-Dihydro-3H- Pyrrolo[2,3-D]Pyrimidin-5-Yl)Methyl)Benzamido)-4-Cyanophenyl)Acetic Acid. (pdb code 6pfh). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 5 binding sites of Fluorine where determined in the Crystal Structure of Ts-Dhfr From Cryptosporidium Hominis in Complex with Nadph, Fdump and 2-(2-(4-((2-Amino-4-Oxo-4,7-Dihydro-3H- Pyrrolo[2,3-D]Pyrimidin-5-Yl)Methyl)Benzamido)-4-Cyanophenyl)Acetic Acid., PDB code: 6pfh:
Jump to Fluorine binding site number: 1; 2; 3; 4; 5;

Fluorine binding site 1 out of 5 in the Crystal Structure of Ts-Dhfr From Cryptosporidium Hominis in Complex with Nadph, Fdump and 2-(2-(4-((2-Amino-4-Oxo-4,7-Dihydro-3H- Pyrrolo[2,3-D]Pyrimidin-5-Yl)Methyl)Benzamido)-4-Cyanophenyl)Acetic Acid.


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Crystal Structure of Ts-Dhfr From Cryptosporidium Hominis in Complex with Nadph, Fdump and 2-(2-(4-((2-Amino-4-Oxo-4,7-Dihydro-3H- Pyrrolo[2,3-D]Pyrimidin-5-Yl)Methyl)Benzamido)-4-Cyanophenyl)Acetic Acid. within 5.0Å range: probe atom residue distance (Å) B Occ A:F602 b:89.2 occ:1.00 F5 A:UFP602 0.0 89.2 1.0 C5 A:UFP602 1.4 72.7 1.0 C6 A:UFP602 2.3 61.9 1.0 C4 A:UFP602 2.4 74.5 1.0 O4 A:UFP602 2.7 59.0 1.0 C5 A:OFD603 3.2 59.5 1.0 C6 A:OFD603 3.3 69.5 1.0 C7 A:OFD603 3.4 72.2 1.0 N1 A:UFP602 3.6 65.7 1.0 N3 A:UFP602 3.6 80.5 1.0 OH A:TYR342 3.6 74.4 1.0 C3 A:OFD603 3.9 70.3 1.0 CH2 A:TRP316 4.0 49.4 1.0 N3 A:OFD603 4.0 73.7 1.0 SG A:CYS402 4.0 73.8 1.0 CZ2 A:TRP316 4.1 67.9 1.0 C2 A:UFP602 4.1 71.5 1.0 C2 A:OFD603 4.3 60.2 1.0 CB A:CYS402 4.3 61.2 1.0 CZ A:TYR342 4.5 73.1 1.0 CD2 A:LEU399 4.6 62.7 1.0 O4' A:UFP602 4.6 63.9 1.0 CE2 A:TYR342 4.7 73.0 1.0 C1' A:UFP602 4.7 56.9 1.0 C4 A:OFD603 4.8 69.4 1.0 C8 A:OFD603 4.9 66.0 1.0 CZ3 A:TRP316 4.9 55.4 1.0

Fluorine binding site 2 out of 5 in the Crystal Structure of Ts-Dhfr From Cryptosporidium Hominis in Complex with Nadph, Fdump and 2-(2-(4-((2-Amino-4-Oxo-4,7-Dihydro-3H- Pyrrolo[2,3-D]Pyrimidin-5-Yl)Methyl)Benzamido)-4-Cyanophenyl)Acetic Acid.


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Crystal Structure of Ts-Dhfr From Cryptosporidium Hominis in Complex with Nadph, Fdump and 2-(2-(4-((2-Amino-4-Oxo-4,7-Dihydro-3H- Pyrrolo[2,3-D]Pyrimidin-5-Yl)Methyl)Benzamido)-4-Cyanophenyl)Acetic Acid. within 5.0Å range: probe atom residue distance (Å) B Occ B:F602 b:0.7 occ:1.00 F5 B:UFP602 0.0 0.7 1.0 C5 B:UFP602 1.4 79.8 1.0 C6 B:UFP602 2.3 70.2 1.0 C4 B:UFP602 2.4 76.3 1.0 O4 B:UFP602 2.7 86.8 1.0 C5 B:OFD603 3.5 73.4 1.0 C6 B:OFD603 3.5 73.7 1.0 N1 B:UFP602 3.6 72.8 1.0 N3 B:UFP602 3.6 82.8 1.0 C7 B:OFD603 3.6 82.2 1.0 OH B:TYR342 3.7 81.6 1.0 SG B:CYS402 4.0 82.4 1.0 C2 B:UFP602 4.1 78.3 1.0 CH2 B:TRP316 4.1 76.6 1.0 N3 B:OFD603 4.1 76.4 1.0 C3 B:OFD603 4.1 72.2 1.0 CZ2 B:TRP316 4.1 96.1 1.0 CB B:CYS402 4.2 66.2 1.0 CE2 B:TYR342 4.3 74.3 1.0 CZ B:TYR342 4.4 71.8 1.0 C2 B:OFD603 4.5 69.6 1.0 O4' B:UFP602 4.6 80.2 1.0 CE1 B:HIS403 4.6 74.7 1.0 CD2 B:LEU399 4.7 78.1 1.0 C1' B:UFP602 4.7 68.3 1.0 ND1 B:HIS403 4.9 78.4 1.0

Fluorine binding site 3 out of 5 in the Crystal Structure of Ts-Dhfr From Cryptosporidium Hominis in Complex with Nadph, Fdump and 2-(2-(4-((2-Amino-4-Oxo-4,7-Dihydro-3H- Pyrrolo[2,3-D]Pyrimidin-5-Yl)Methyl)Benzamido)-4-Cyanophenyl)Acetic Acid.


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Crystal Structure of Ts-Dhfr From Cryptosporidium Hominis in Complex with Nadph, Fdump and 2-(2-(4-((2-Amino-4-Oxo-4,7-Dihydro-3H- Pyrrolo[2,3-D]Pyrimidin-5-Yl)Methyl)Benzamido)-4-Cyanophenyl)Acetic Acid. within 5.0Å range: probe atom residue distance (Å) B Occ C:F602 b:0.5 occ:1.00 F5 C:UFP602 0.0 0.5 1.0 C5 C:UFP602 1.4 0.9 1.0 C6 C:UFP602 2.3 0.1 1.0 C4 C:UFP602 2.4 0.9 1.0 O4 C:UFP602 2.7 0.7 1.0 C6 C:OFD603 3.3 0.2 1.0 C5 C:OFD603 3.3 0.1 1.0 C7 C:OFD603 3.5 0.5 1.0 N1 C:UFP602 3.6 0.4 1.0 N3 C:UFP602 3.6 0.2 1.0 OH C:TYR342 3.8 0.3 1.0 N3 C:OFD603 4.0 1.0 1.0 C3 C:OFD603 4.0 0.8 1.0 C2 C:UFP602 4.1 99.4 1.0 CH2 C:TRP316 4.1 88.7 1.0 SG C:CYS402 4.1 0.3 1.0 CZ2 C:TRP316 4.2 0.5 1.0 CB C:CYS402 4.4 79.4 1.0 C2 C:OFD603 4.4 0.1 1.0 CE2 C:TYR342 4.4 97.6 1.0 CZ C:TYR342 4.5 92.7 1.0 CE1 C:HIS403 4.6 97.1 1.0 O4' C:UFP602 4.6 0.7 1.0 CD2 C:LEU399 4.7 96.3 1.0 C1' C:UFP602 4.7 0.6 1.0 ND1 C:HIS403 4.9 0.8 1.0 C4 C:OFD603 5.0 0.4 1.0 C8 C:OFD603 5.0 96.2 1.0

Fluorine binding site 4 out of 5 in the Crystal Structure of Ts-Dhfr From Cryptosporidium Hominis in Complex with Nadph, Fdump and 2-(2-(4-((2-Amino-4-Oxo-4,7-Dihydro-3H- Pyrrolo[2,3-D]Pyrimidin-5-Yl)Methyl)Benzamido)-4-Cyanophenyl)Acetic Acid.


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 4 of Crystal Structure of Ts-Dhfr From Cryptosporidium Hominis in Complex with Nadph, Fdump and 2-(2-(4-((2-Amino-4-Oxo-4,7-Dihydro-3H- Pyrrolo[2,3-D]Pyrimidin-5-Yl)Methyl)Benzamido)-4-Cyanophenyl)Acetic Acid. within 5.0Å range: probe atom residue distance (Å) B Occ D:F602 b:98.1 occ:1.00 F5 D:UFP602 0.0 98.1 1.0 C5 D:UFP602 1.4 70.5 1.0 C6 D:UFP602 2.3 60.6 1.0 C4 D:UFP602 2.4 77.1 1.0 O4 D:UFP602 2.7 68.2 1.0 C6 D:OFD603 3.2 68.5 1.0 C5 D:OFD603 3.2 64.9 1.0 C7 D:OFD603 3.5 79.9 1.0 N1 D:UFP602 3.6 73.9 1.0 N3 D:UFP602 3.6 75.4 1.0 OH D:TYR342 3.8 72.2 1.0 N3 D:OFD603 3.9 71.7 1.0 C3 D:OFD603 4.0 68.0 1.0 SG D:CYS402 4.0 69.8 1.0 CH2 D:TRP316 4.1 51.7 1.0 C2 D:UFP602 4.1 74.3 1.0 CZ2 D:TRP316 4.1 60.0 1.0 C2 D:OFD603 4.3 62.5 1.0 CB D:CYS402 4.3 58.6 1.0 CD2 D:LEU399 4.4 62.0 1.0 CE2 D:TYR342 4.4 78.6 1.0 CZ D:TYR342 4.5 70.9 1.0 O4' D:UFP602 4.6 69.2 1.0 C1' D:UFP602 4.7 60.1 1.0 C4 D:OFD603 4.9 72.6 1.0 C8 D:OFD603 4.9 74.2 1.0

Fluorine binding site 5 out of 5 in the Crystal Structure of Ts-Dhfr From Cryptosporidium Hominis in Complex with Nadph, Fdump and 2-(2-(4-((2-Amino-4-Oxo-4,7-Dihydro-3H- Pyrrolo[2,3-D]Pyrimidin-5-Yl)Methyl)Benzamido)-4-Cyanophenyl)Acetic Acid.


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 5 of Crystal Structure of Ts-Dhfr From Cryptosporidium Hominis in Complex with Nadph, Fdump and 2-(2-(4-((2-Amino-4-Oxo-4,7-Dihydro-3H- Pyrrolo[2,3-D]Pyrimidin-5-Yl)Methyl)Benzamido)-4-Cyanophenyl)Acetic Acid. within 5.0Å range: probe atom residue distance (Å) B Occ E:F602 b:0.1 occ:1.00 F5 E:UFP602 0.0 0.1 1.0 C5 E:UFP602 1.4 87.0 1.0 C6 E:UFP602 2.3 79.1 1.0 C4 E:UFP602 2.4 82.7 1.0 O4 E:UFP602 2.7 73.7 1.0 C5 E:OFD603 3.3 85.8 1.0 C6 E:OFD603 3.4 83.5 1.0 C7 E:OFD603 3.5 85.4 1.0 N1 E:UFP602 3.6 81.8 1.0 N3 E:UFP602 3.6 80.1 1.0 OH E:TYR342 3.9 83.6 1.0 C3 E:OFD603 4.0 89.2 1.0 SG E:CYS402 4.0 91.0 1.0 N3 E:OFD603 4.0 79.1 1.0 CH2 E:TRP316 4.1 79.1 1.0 C2 E:UFP602 4.1 78.9 1.0 CZ2 E:TRP316 4.1 87.1 1.0 CB E:CYS402 4.3 68.6 1.0 C2 E:OFD603 4.4 75.7 1.0 CE2 E:TYR342 4.4 80.7 1.0 CZ E:TYR342 4.6 71.2 1.0 O4' E:UFP602 4.6 83.2 1.0 CD2 E:LEU399 4.7 81.1 1.0 CE1 E:HIS403 4.7 80.5 1.0 C1' E:UFP602 4.7 71.9 1.0 C4 E:OFD603 4.9 86.7 1.0 C8 E:OFD603 5.0 85.7 1.0 ND1 E:HIS403 5.0 78.3 1.0

D.J.Czyzyk, M.Valhondo, L.Deiana, J.Tirado-Rives, W.L.Jorgensen, K.S.Anderson. Structure Activity Relationship Towards Design of Cryptosporidium Specific Thymidylate Synthase Inhibitors. Eur.J.Med.Chem. V. 183 11673 2019.
ISSN: ISSN 0223-5234
PubMed: 31536894
DOI: 10.1016/J.EJMECH.2019.111673