Fluorine in PDB 6w0w: Structure of Khk in Complex with Compound 3

All present enzymatic activity of Structure of Khk in Complex with Compound 3:
2.7.1.3;

The structure of Structure of Khk in Complex with Compound 3, PDB code: 6w0w was solved by J.Jasti, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	31.42 / 2.80
Space group	P 21 21 21
Cell size a, b, c (Å), α, β, γ (°)	83.190, 85.250, 139.470, 90.00, 90.00, 90.00
R / Rfree (%)	17.9 / 21.6

The binding sites of Fluorine atom in the Structure of Khk in Complex with Compound 3 (pdb code 6w0w). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 6 binding sites of Fluorine where determined in the Structure of Khk in Complex with Compound 3, PDB code: 6w0w:
Jump to Fluorine binding site number: 1; 2; 3; 4; 5; 6;

Fluorine binding site 1 out of 6 in the Structure of Khk in Complex with Compound 3


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Structure of Khk in Complex with Compound 3 within 5.0Å range: probe atom residue distance (Å) B Occ A:F301 b:93.2 occ:1.00 F1 A:RZA301 0.0 93.2 1.0 C14 A:RZA301 1.3 88.8 1.0 F2 A:RZA301 2.1 84.2 1.0 F3 A:RZA301 2.1 92.5 1.0 C7 A:RZA301 2.4 85.4 1.0 C8 A:RZA301 2.7 88.8 1.0 C6 A:RZA301 3.6 81.7 1.0 CG2 A:VAL250 3.8 65.0 1.0 SG A:CYS289 3.9 74.0 1.0 CG1 A:VAL250 3.9 66.1 1.0 CB A:CYS289 3.9 69.6 1.0 CD A:PRO247 4.0 62.4 1.0 C9 A:RZA301 4.1 91.4 1.0 C15 A:RZA301 4.2 80.4 1.0 OE2 A:GLU227 4.2 0.0 1.0 CB A:VAL250 4.5 66.0 1.0 CA A:PRO246 4.7 55.6 1.0 CB A:PRO246 4.7 55.8 1.0 C5 A:RZA301 4.7 83.1 1.0 CG2 A:THR253 4.8 84.0 1.0 CG A:PRO247 4.9 66.5 1.0 N2 A:RZA301 4.9 87.8 1.0 N4 A:RZA301 4.9 80.1 1.0 N3 A:RZA301 5.0 97.2 1.0

Fluorine binding site 2 out of 6 in the Structure of Khk in Complex with Compound 3


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Structure of Khk in Complex with Compound 3 within 5.0Å range: probe atom residue distance (Å) B Occ A:F301 b:84.2 occ:1.00 F2 A:RZA301 0.0 84.2 1.0 C14 A:RZA301 1.3 88.8 1.0 F1 A:RZA301 2.1 93.2 1.0 F3 A:RZA301 2.1 92.5 1.0 C7 A:RZA301 2.4 85.4 1.0 C6 A:RZA301 3.2 81.7 1.0 C8 A:RZA301 3.2 88.8 1.0 CB A:GLU227 3.4 76.1 1.0 C15 A:RZA301 3.5 80.4 1.0 CA A:GLU227 3.6 74.9 1.0 CB A:PRO246 3.8 55.8 1.0 OE2 A:GLU227 3.9 0.0 1.0 CA A:PRO246 4.1 55.6 1.0 N4 A:RZA301 4.1 80.1 1.0 N A:GLU227 4.2 76.0 1.0 C5 A:RZA301 4.4 83.1 1.0 C9 A:RZA301 4.4 91.4 1.0 CB A:ALA244 4.5 57.0 1.0 CG A:GLU227 4.5 87.8 1.0 CD A:GLU227 4.6 0.9 1.0 N A:PRO246 4.7 55.9 1.0 CG A:PRO246 4.7 59.5 1.0 CD A:PRO247 4.8 62.4 1.0 C A:GLU227 4.8 78.6 1.0 N2 A:RZA301 4.9 87.8 1.0 C A:ALA226 4.9 81.4 1.0 CD A:PRO246 4.9 56.7 1.0

Fluorine binding site 3 out of 6 in the Structure of Khk in Complex with Compound 3


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Structure of Khk in Complex with Compound 3 within 5.0Å range: probe atom residue distance (Å) B Occ A:F301 b:92.5 occ:1.00 F3 A:RZA301 0.0 92.5 1.0 C14 A:RZA301 1.3 88.8 1.0 F1 A:RZA301 2.1 93.2 1.0 F2 A:RZA301 2.1 84.2 1.0 C7 A:RZA301 2.4 85.4 1.0 C15 A:RZA301 2.7 80.4 1.0 C6 A:RZA301 2.9 81.7 1.0 N4 A:RZA301 3.1 80.1 1.0 CA A:PRO246 3.2 55.6 1.0 CD A:PRO247 3.4 62.4 1.0 C8 A:RZA301 3.6 88.8 1.0 CB A:PRO246 3.8 55.8 1.0 N A:PRO246 3.9 55.9 1.0 CA A:GLY286 3.9 57.9 1.0 O A:PHE245 4.0 60.8 1.0 N A:PRO247 4.2 60.9 1.0 C A:PHE245 4.2 59.9 1.0 CB A:CYS289 4.2 69.6 1.0 C A:PRO246 4.2 63.6 1.0 SG A:CYS289 4.2 74.0 1.0 C5 A:RZA301 4.3 83.1 1.0 O A:GLY286 4.6 65.4 1.0 CG A:PRO247 4.6 66.5 1.0 CD A:PRO246 4.7 56.7 1.0 C9 A:RZA301 4.8 91.4 1.0 C A:GLY286 4.8 64.0 1.0 N A:GLY286 4.8 59.4 1.0 CB A:ALA244 4.9 57.0 1.0 CG A:PRO246 4.9 59.5 1.0 CG2 A:VAL250 5.0 65.0 1.0

Fluorine binding site 4 out of 6 in the Structure of Khk in Complex with Compound 3


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 4 of Structure of Khk in Complex with Compound 3 within 5.0Å range: probe atom residue distance (Å) B Occ B:F301 b:0.0 occ:1.00 F1 B:RZA301 0.0 0.0 1.0 C14 B:RZA301 1.3 0.7 1.0 F3 B:RZA301 2.1 0.6 1.0 F2 B:RZA301 2.1 0.4 1.0 C7 B:RZA301 2.4 91.0 1.0 C8 B:RZA301 2.7 86.3 1.0 CG2 B:VAL250 3.6 76.7 1.0 C6 B:RZA301 3.6 85.8 1.0 CD B:PRO247 3.8 77.0 1.0 CB B:CYS289 3.9 72.8 1.0 SG B:CYS289 3.9 77.2 1.0 C9 B:RZA301 4.1 86.2 1.0 C15 B:RZA301 4.2 84.4 1.0 OE1 B:GLU227 4.2 97.6 1.0 CG1 B:VAL250 4.6 76.4 1.0 CA B:PRO246 4.6 69.3 1.0 CG B:PRO247 4.7 82.0 1.0 C5 B:RZA301 4.7 84.4 1.0 CB B:VAL250 4.7 77.6 1.0 CB B:PRO246 4.7 70.2 1.0 CG2 B:THR253 4.8 72.5 1.0 N2 B:RZA301 4.9 85.2 1.0 N4 B:RZA301 4.9 83.9 1.0 N3 B:RZA301 5.0 89.9 1.0

Fluorine binding site 5 out of 6 in the Structure of Khk in Complex with Compound 3


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 5 of Structure of Khk in Complex with Compound 3 within 5.0Å range: probe atom residue distance (Å) B Occ B:F301 b:0.4 occ:1.00 F2 B:RZA301 0.0 0.4 1.0 C14 B:RZA301 1.3 0.7 1.0 F1 B:RZA301 2.1 0.0 1.0 F3 B:RZA301 2.1 0.6 1.0 C7 B:RZA301 2.4 91.0 1.0 C8 B:RZA301 3.2 86.3 1.0 C6 B:RZA301 3.2 85.8 1.0 C15 B:RZA301 3.5 84.4 1.0 CB B:GLU227 3.6 73.6 1.0 CB B:PRO246 3.8 70.2 1.0 OE1 B:GLU227 3.8 97.6 1.0 CA B:GLU227 3.9 71.5 1.0 CA B:PRO246 4.0 69.3 1.0 N4 B:RZA301 4.1 83.9 1.0 C9 B:RZA301 4.4 86.2 1.0 C5 B:RZA301 4.5 84.4 1.0 N B:GLU227 4.5 70.7 1.0 CB B:ALA244 4.5 62.7 1.0 N B:PRO246 4.6 68.5 1.0 CD B:GLU227 4.6 0.8 1.0 CG B:GLU227 4.6 89.0 1.0 CD B:PRO247 4.7 77.0 1.0 CG B:PRO246 4.8 74.2 1.0 CD B:PRO246 4.8 70.5 1.0 N2 B:RZA301 4.9 85.2 1.0

Fluorine binding site 6 out of 6 in the Structure of Khk in Complex with Compound 3


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 6 of Structure of Khk in Complex with Compound 3 within 5.0Å range: probe atom residue distance (Å) B Occ B:F301 b:0.6 occ:1.00 F3 B:RZA301 0.0 0.6 1.0 C14 B:RZA301 1.3 0.7 1.0 F1 B:RZA301 2.1 0.0 1.0 F2 B:RZA301 2.1 0.4 1.0 C7 B:RZA301 2.4 91.0 1.0 C15 B:RZA301 2.7 84.4 1.0 C6 B:RZA301 2.9 85.8 1.0 N4 B:RZA301 3.1 83.9 1.0 CD B:PRO247 3.2 77.0 1.0 CA B:PRO246 3.2 69.3 1.0 C8 B:RZA301 3.6 86.3 1.0 CB B:PRO246 3.8 70.2 1.0 N B:PRO246 3.9 68.5 1.0 CA B:GLY286 3.9 56.9 1.0 O B:PHE245 4.0 68.8 1.0 N B:PRO247 4.1 76.5 1.0 CB B:CYS289 4.1 72.8 1.0 C B:PHE245 4.2 69.6 1.0 C B:PRO246 4.2 78.3 1.0 SG B:CYS289 4.2 77.2 1.0 C5 B:RZA301 4.3 84.4 1.0 CG B:PRO247 4.4 82.0 1.0 O B:GLY286 4.5 64.6 1.0 C9 B:RZA301 4.7 86.2 1.0 C B:GLY286 4.7 64.0 1.0 CD B:PRO246 4.8 70.5 1.0 N B:GLY286 4.9 56.5 1.0 CG2 B:VAL250 5.0 76.7 1.0 CG B:PRO246 5.0 74.2 1.0 CB B:ALA244 5.0 62.7 1.0

K.Futatsugi, A.C.Smith, M.Tu, B.Raymer, K.Ahn, S.B.Coffey, M.S.Dowling, D.P.Fernando, J.A.Gutierrez, K.Huard, J.Jasti, A.S.Kalgutkar, J.D.Knafels, J.Pandit, K.D.Parris, S.Perez, J.A.Pfefferkorn, D.A.Price, T.Ryder, A.Shavnya, I.A.Stock, A.S.Tsai, G.J.Tesz, B.A.Thuma, Y.Weng, H.M.Wisniewska, G.Xing, J.Zhou, T.V.Magee. Discovery of Pf-06835919: A Potent Inhibitor of Ketohexokinase (Khk) For the Treatment of Metabolic Disorders Driven By the Overconsumption of Fructose. J.Med.Chem. V. 63 13546 2020.
ISSN: ISSN 0022-2623
PubMed: 32910646
DOI: 10.1021/ACS.JMEDCHEM.0C00944