Fluorine in PDB 2r4f: Substituted Pyrazoles As Hepatselective Hmg-Coa Reductase Inhibitors

All present enzymatic activity of Substituted Pyrazoles As Hepatselective Hmg-Coa Reductase Inhibitors:
1.1.1.34;

The structure of Substituted Pyrazoles As Hepatselective Hmg-Coa Reductase Inhibitors, PDB code: 2r4f was solved by A.Pavlovsky, J.A.Pfefferkorn, M.S.Harris, B.C.Finzel, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	39.54 / 1.70
Space group	P 1 21 1
Cell size a, b, c (Å), α, β, γ (°)	82.616, 135.334, 82.844, 90.00, 97.53, 90.00
R / Rfree (%)	21.4 / 23.4

The binding sites of Fluorine atom in the Substituted Pyrazoles As Hepatselective Hmg-Coa Reductase Inhibitors (pdb code 2r4f). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 4 binding sites of Fluorine where determined in the Substituted Pyrazoles As Hepatselective Hmg-Coa Reductase Inhibitors, PDB code: 2r4f:
Jump to Fluorine binding site number: 1; 2; 3; 4;

Fluorine binding site 1 out of 4 in the Substituted Pyrazoles As Hepatselective Hmg-Coa Reductase Inhibitors


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Substituted Pyrazoles As Hepatselective Hmg-Coa Reductase Inhibitors within 5.0Å range: probe atom residue distance (Å) B Occ A:F876 b:23.2 occ:1.00 F1 A:RIE876 0.0 23.2 1.0 C30 A:RIE876 1.3 22.8 1.0 C15 A:RIE876 2.4 22.8 1.0 C24 A:RIE876 2.4 23.2 1.0 OG A:SER661 2.9 23.5 1.0 O A:HOH1129 3.0 53.0 1.0 CB A:SER661 3.2 23.6 1.0 NH1 A:ARG590 3.3 21.0 1.0 CG1 A:VAL683 3.3 19.0 1.0 NE A:ARG590 3.4 19.8 1.0 CZ A:ARG590 3.6 20.2 1.0 C18 A:RIE876 3.6 22.8 1.0 C21 A:RIE876 3.6 22.7 1.0 C27 A:RIE876 4.2 22.1 1.0 CG2 A:VAL683 4.3 18.9 1.0 O A:HOH917 4.3 34.1 1.0 CA A:SER661 4.4 23.6 1.0 CB A:VAL683 4.4 18.6 1.0 CD A:ARG590 4.4 18.9 1.0 NH2 A:ARG590 4.7 19.6 1.0 CG A:ARG590 4.9 17.4 1.0

Fluorine binding site 2 out of 4 in the Substituted Pyrazoles As Hepatselective Hmg-Coa Reductase Inhibitors


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Substituted Pyrazoles As Hepatselective Hmg-Coa Reductase Inhibitors within 5.0Å range: probe atom residue distance (Å) B Occ B:F876 b:24.0 occ:1.00 F1 B:RIE876 0.0 24.0 1.0 C30 B:RIE876 1.3 23.8 1.0 C24 B:RIE876 2.4 23.9 1.0 C15 B:RIE876 2.4 24.0 1.0 OG B:SER661 2.9 25.6 1.0 CB B:SER661 3.3 25.4 1.0 NH1 B:ARG590 3.3 21.8 1.0 NE B:ARG590 3.4 21.1 1.0 CG1 B:VAL683 3.4 19.2 1.0 CZ B:ARG590 3.6 21.2 1.0 C21 B:RIE876 3.6 23.7 1.0 C18 B:RIE876 3.6 23.8 1.0 O B:HOH1184 4.1 31.8 1.0 C27 B:RIE876 4.2 23.2 1.0 CG2 B:VAL683 4.3 19.1 1.0 CD B:ARG590 4.4 19.9 1.0 CA B:SER661 4.5 25.3 1.0 CB B:VAL683 4.5 19.0 1.0 NH2 B:ARG590 4.6 20.6 1.0 CG B:ARG590 4.9 18.6 1.0

Fluorine binding site 3 out of 4 in the Substituted Pyrazoles As Hepatselective Hmg-Coa Reductase Inhibitors


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Substituted Pyrazoles As Hepatselective Hmg-Coa Reductase Inhibitors within 5.0Å range: probe atom residue distance (Å) B Occ C:F876 b:22.2 occ:1.00 F1 C:RIE876 0.0 22.2 1.0 C30 C:RIE876 1.3 21.7 1.0 C24 C:RIE876 2.4 21.8 1.0 C15 C:RIE876 2.4 21.8 1.0 OG C:SER661 2.9 27.0 1.0 NH2 C:ARG590 3.0 21.4 1.0 CB C:SER661 3.4 26.7 1.0 CG1 C:VAL683 3.4 17.9 1.0 CD C:ARG590 3.6 20.3 1.0 C21 C:RIE876 3.6 21.6 1.0 C18 C:RIE876 3.6 21.6 1.0 CZ C:ARG590 3.8 20.8 1.0 NE C:ARG590 4.0 20.7 1.0 C27 C:RIE876 4.2 21.1 1.0 CG2 C:VAL683 4.3 17.7 1.0 CB C:VAL683 4.5 17.7 1.0 O C:HOH946 4.5 32.2 1.0 CA C:SER661 4.5 26.7 1.0 O C:HOH1132 4.6 44.3 1.0 CG C:ARG590 4.8 18.8 1.0 NH1 C:ARG590 4.9 20.0 1.0

Fluorine binding site 4 out of 4 in the Substituted Pyrazoles As Hepatselective Hmg-Coa Reductase Inhibitors


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 4 of Substituted Pyrazoles As Hepatselective Hmg-Coa Reductase Inhibitors within 5.0Å range: probe atom residue distance (Å) B Occ D:F876 b:22.6 occ:1.00 F1 D:RIE876 0.0 22.6 1.0 C30 D:RIE876 1.3 22.1 1.0 C15 D:RIE876 2.4 22.5 1.0 C24 D:RIE876 2.4 22.5 1.0 OG D:SER661 2.9 26.7 1.0 CB D:SER661 3.3 26.6 1.0 NE D:ARG590 3.3 19.9 1.0 CG1 D:VAL683 3.4 18.8 1.0 NH1 D:ARG590 3.4 20.5 1.0 CZ D:ARG590 3.6 19.8 1.0 C21 D:RIE876 3.6 22.0 1.0 C18 D:RIE876 3.6 22.1 1.0 C27 D:RIE876 4.2 21.4 1.0 CG2 D:VAL683 4.2 18.6 1.0 CD D:ARG590 4.3 19.2 1.0 CB D:VAL683 4.4 18.4 1.0 CA D:SER661 4.5 26.6 1.0 O D:HOH1189 4.6 38.4 1.0 NH2 D:ARG590 4.7 19.0 1.0 O D:HOH1270 4.7 50.1 1.0 CG D:ARG590 4.7 18.0 1.0

J.A.Pfefferkorn, C.Choi, S.D.Larsen, B.Auerbach, R.Hutchings, W.Park, V.Askew, L.Dillon, J.C.Hanselman, Z.Lin, G.H.Lu, A.Robertson, C.Sekerke, M.S.Harris, A.Pavlovsky, G.Bainbridge, N.Caspers, M.Kowala, B.D.Tait. Substituted Pyrazoles As Hepatoselective Hmg-Coa Reductase Inhibitors: Discovery of (3R,5R)-7-[2-(4-Fluoro-Phenyl)-4-Isopropyl-5-(4- Methyl-Benzylcarbamoyl)-2H-Pyrazol-3-Yl]-3,5- Dihydroxyheptanoic Acid (Pf-3052334) As A Candidate For the Treatment of Hypercholesterolemia. J.Med.Chem. V. 51 31 2008.
ISSN: ISSN 0022-2623
PubMed: 18072721
DOI: 10.1021/JM070849R