Fluorine in PDB 6w0z: Structure of Khk in Complex with Compound 8 (2-[(1~{S},5~{R})-3-[2- [(2~{S})-2-Methylazetidin-1-Yl]-6-(Trifluoromethyl)Pyrimidin-4-Yl]-3- Azabicyclo[3.1.0]Hexan-6-Yl]Ethanoic Acid)

Enzymatic activity of Structure of Khk in Complex with Compound 8 (2-[(1~{S},5~{R})-3-[2- [(2~{S})-2-Methylazetidin-1-Yl]-6-(Trifluoromethyl)Pyrimidin-4-Yl]-3- Azabicyclo[3.1.0]Hexan-6-Yl]Ethanoic Acid)

All present enzymatic activity of Structure of Khk in Complex with Compound 8 (2-[(1~{S},5~{R})-3-[2- [(2~{S})-2-Methylazetidin-1-Yl]-6-(Trifluoromethyl)Pyrimidin-4-Yl]-3- Azabicyclo[3.1.0]Hexan-6-Yl]Ethanoic Acid):
2.7.1.3;

Protein crystallography data

The structure of Structure of Khk in Complex with Compound 8 (2-[(1~{S},5~{R})-3-[2- [(2~{S})-2-Methylazetidin-1-Yl]-6-(Trifluoromethyl)Pyrimidin-4-Yl]-3- Azabicyclo[3.1.0]Hexan-6-Yl]Ethanoic Acid), PDB code: 6w0z was solved by J.Jasti, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å) 22.95 / 2.30
Space group P 21 21 21
Cell size a, b, c (Å), α, β, γ (°) 82.415, 82.883, 137.186, 90.00, 90.00, 90.00
R / Rfree (%) 18 / 19.5

Fluorine Binding Sites:

The binding sites of Fluorine atom in the Structure of Khk in Complex with Compound 8 (2-[(1~{S},5~{R})-3-[2- [(2~{S})-2-Methylazetidin-1-Yl]-6-(Trifluoromethyl)Pyrimidin-4-Yl]-3- Azabicyclo[3.1.0]Hexan-6-Yl]Ethanoic Acid) (pdb code 6w0z). 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 8 (2-[(1~{S},5~{R})-3-[2- [(2~{S})-2-Methylazetidin-1-Yl]-6-(Trifluoromethyl)Pyrimidin-4-Yl]-3- Azabicyclo[3.1.0]Hexan-6-Yl]Ethanoic Acid), PDB code: 6w0z:
Jump to Fluorine binding site number: 1; 2; 3; 4; 5; 6;

Fluorine binding site 1 out of 6 in 6w0z

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Fluorine binding site 1 out of 6 in the Structure of Khk in Complex with Compound 8 (2-[(1~{S},5~{R})-3-[2- [(2~{S})-2-Methylazetidin-1-Yl]-6-(Trifluoromethyl)Pyrimidin-4-Yl]-3- Azabicyclo[3.1.0]Hexan-6-Yl]Ethanoic Acid)


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 8 (2-[(1~{S},5~{R})-3-[2- [(2~{S})-2-Methylazetidin-1-Yl]-6-(Trifluoromethyl)Pyrimidin-4-Yl]-3- Azabicyclo[3.1.0]Hexan-6-Yl]Ethanoic Acid) within 5.0Å range:
probe atom residue distance (Å) B Occ
A:F301

b:59.5
occ:1.00
 F1 A:S6D301 0.0 59.5 1.0
C16 A:S6D301 1.3 55.1 1.0
F2 A:S6D301 2.1 54.9 1.0
F3 A:S6D301 2.1 56.1 1.0
C6 A:S6D301 2.4 49.7 1.0
N2 A:S6D301 2.8 47.8 1.0
C7 A:S6D301 3.5 45.8 1.0
CB A:ALA244 3.5 41.4 1.0
CA A:PRO246 3.5 39.2 1.0
CB A:PRO246 3.5 40.4 1.0
CB A:GLU227 3.5 49.2 1.0
O A:HOH409 3.6 39.6 1.0
CA A:GLU227 3.7 47.2 1.0
N A:PRO246 3.7 39.5 1.0
CD A:PRO246 3.9 40.2 1.0
C5 A:S6D301 4.1 47.9 1.0
CG A:PRO246 4.3 44.3 1.0
C A:PHE245 4.3 41.1 1.0
N A:GLU227 4.4 47.3 1.0
N A:PHE245 4.4 38.0 1.0
C8 A:S6D301 4.6 47.5 1.0
O A:ALA226 4.6 50.4 1.0
CA A:ALA244 4.7 40.9 1.0
O A:PHE245 4.7 38.1 1.0
C A:GLU227 4.7 48.6 1.0
C A:ALA226 4.8 51.5 1.0
O A:GLU227 4.8 47.5 1.0
C A:ALA244 4.8 42.3 1.0
N3 A:S6D301 4.8 45.9 1.0
CG A:GLU227 4.9 64.1 1.0
C A:PRO246 4.9 43.7 1.0
CD A:PRO247 4.9 43.1 1.0
N1 A:S6D301 5.0 48.3 1.0

Fluorine binding site 2 out of 6 in 6w0z

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Fluorine binding site 2 out of 6 in the Structure of Khk in Complex with Compound 8 (2-[(1~{S},5~{R})-3-[2- [(2~{S})-2-Methylazetidin-1-Yl]-6-(Trifluoromethyl)Pyrimidin-4-Yl]-3- Azabicyclo[3.1.0]Hexan-6-Yl]Ethanoic Acid)


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 8 (2-[(1~{S},5~{R})-3-[2- [(2~{S})-2-Methylazetidin-1-Yl]-6-(Trifluoromethyl)Pyrimidin-4-Yl]-3- Azabicyclo[3.1.0]Hexan-6-Yl]Ethanoic Acid) within 5.0Å range:
probe atom residue distance (Å) B Occ
A:F301

b:54.9
occ:1.00
 F2 A:S6D301 0.0 54.9 1.0
C16 A:S6D301 1.3 55.1 1.0
F3 A:S6D301 2.1 56.1 1.0
F1 A:S6D301 2.1 59.5 1.0
C6 A:S6D301 2.3 49.7 1.0
N2 A:S6D301 2.8 47.8 1.0
CA A:GLY286 3.3 39.4 1.0
O A:HOH409 3.4 39.6 1.0
C7 A:S6D301 3.4 45.8 1.0
CA A:PRO246 3.5 39.2 1.0
CD A:PRO247 3.7 43.1 1.0
SG A:CYS289 3.8 48.1 1.0
O A:PHE245 3.8 38.1 1.0
CB A:CYS289 3.9 44.3 1.0
N A:PRO246 3.9 39.5 1.0
O A:GLY286 4.1 45.1 1.0
C A:PHE245 4.1 41.1 1.0
C5 A:S6D301 4.1 47.9 1.0
N A:GLY286 4.1 38.9 1.0
C A:GLY286 4.2 44.2 1.0
CB A:PRO246 4.2 40.4 1.0
O A:ALA285 4.4 45.1 1.0
C A:PRO246 4.5 43.7 1.0
N A:PRO247 4.5 42.1 1.0
C8 A:S6D301 4.5 47.5 1.0
C A:ALA285 4.6 43.9 1.0
N A:PHE245 4.8 38.0 1.0
N3 A:S6D301 4.8 45.9 1.0
CD A:PRO246 4.9 40.2 1.0
CB A:ALA244 5.0 41.4 1.0
CG A:PRO247 5.0 47.2 1.0

Fluorine binding site 3 out of 6 in 6w0z

Go back to Fluorine Binding Sites List in 6w0z
Fluorine binding site 3 out of 6 in the Structure of Khk in Complex with Compound 8 (2-[(1~{S},5~{R})-3-[2- [(2~{S})-2-Methylazetidin-1-Yl]-6-(Trifluoromethyl)Pyrimidin-4-Yl]-3- Azabicyclo[3.1.0]Hexan-6-Yl]Ethanoic Acid)


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 8 (2-[(1~{S},5~{R})-3-[2- [(2~{S})-2-Methylazetidin-1-Yl]-6-(Trifluoromethyl)Pyrimidin-4-Yl]-3- Azabicyclo[3.1.0]Hexan-6-Yl]Ethanoic Acid) within 5.0Å range:
probe atom residue distance (Å) B Occ
A:F301

b:56.1
occ:1.00
 F3 A:S6D301 0.0 56.1 1.0
C16 A:S6D301 1.3 55.1 1.0
F2 A:S6D301 2.1 54.9 1.0
F1 A:S6D301 2.1 59.5 1.0
C6 A:S6D301 2.4 49.7 1.0
C7 A:S6D301 2.7 45.8 1.0
N2 A:S6D301 3.5 47.8 1.0
SG A:CYS289 4.0 48.1 1.0
CA A:PRO246 4.1 39.2 1.0
CB A:PRO246 4.1 40.4 1.0
C8 A:S6D301 4.1 47.5 1.0
CD A:PRO247 4.1 43.1 1.0
CB A:GLU227 4.2 49.2 1.0
CB A:CYS289 4.2 44.3 1.0
CG2 A:VAL250 4.3 47.6 1.0
C5 A:S6D301 4.6 47.9 1.0
CA A:GLU227 4.7 47.2 1.0
N A:PRO246 4.9 39.5 1.0
N3 A:S6D301 4.9 45.9 1.0

Fluorine binding site 4 out of 6 in 6w0z

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Fluorine binding site 4 out of 6 in the Structure of Khk in Complex with Compound 8 (2-[(1~{S},5~{R})-3-[2- [(2~{S})-2-Methylazetidin-1-Yl]-6-(Trifluoromethyl)Pyrimidin-4-Yl]-3- Azabicyclo[3.1.0]Hexan-6-Yl]Ethanoic Acid)


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 8 (2-[(1~{S},5~{R})-3-[2- [(2~{S})-2-Methylazetidin-1-Yl]-6-(Trifluoromethyl)Pyrimidin-4-Yl]-3- Azabicyclo[3.1.0]Hexan-6-Yl]Ethanoic Acid) within 5.0Å range:
probe atom residue distance (Å) B Occ
B:F301

b:63.7
occ:1.00
 F1 B:S6D301 0.0 63.7 1.0
C16 B:S6D301 1.3 65.1 1.0
F2 B:S6D301 2.1 70.9 1.0
F3 B:S6D301 2.2 68.2 1.0
C6 B:S6D301 2.4 55.1 1.0
N2 B:S6D301 2.8 49.0 1.0
C7 B:S6D301 3.5 49.8 1.0
CB B:ALA244 3.5 43.5 1.0
CB B:GLU227 3.5 49.5 1.0
CA B:PRO246 3.5 45.1 1.0
CB B:PRO246 3.6 47.1 1.0
O B:HOH443 3.7 40.3 1.0
CA B:GLU227 3.7 47.1 1.0
N B:PRO246 3.7 45.6 1.0
CD B:PRO246 4.0 47.2 1.0
O B:HOH490 4.0 51.3 1.0
C5 B:S6D301 4.1 49.1 1.0
CG B:PRO246 4.3 50.7 1.0
C B:PHE245 4.4 49.8 1.0
N B:GLU227 4.4 45.3 1.0
N B:PHE245 4.5 46.4 1.0
C8 B:S6D301 4.6 50.0 1.0
O B:ALA226 4.7 43.6 1.0
OE1 B:GLU227 4.7 69.3 1.0
CA B:ALA244 4.7 43.4 1.0
O B:PHE245 4.8 49.6 1.0
C B:GLU227 4.8 49.4 1.0
C B:ALA226 4.8 44.8 1.0
O B:GLU227 4.8 47.4 1.0
C B:ALA244 4.8 48.0 1.0
CG B:GLU227 4.8 61.2 1.0
N3 B:S6D301 4.9 50.8 1.0
CD B:PRO247 4.9 47.8 1.0
C B:PRO246 5.0 49.0 1.0

Fluorine binding site 5 out of 6 in 6w0z

Go back to Fluorine Binding Sites List in 6w0z
Fluorine binding site 5 out of 6 in the Structure of Khk in Complex with Compound 8 (2-[(1~{S},5~{R})-3-[2- [(2~{S})-2-Methylazetidin-1-Yl]-6-(Trifluoromethyl)Pyrimidin-4-Yl]-3- Azabicyclo[3.1.0]Hexan-6-Yl]Ethanoic Acid)


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 8 (2-[(1~{S},5~{R})-3-[2- [(2~{S})-2-Methylazetidin-1-Yl]-6-(Trifluoromethyl)Pyrimidin-4-Yl]-3- Azabicyclo[3.1.0]Hexan-6-Yl]Ethanoic Acid) within 5.0Å range:
probe atom residue distance (Å) B Occ
B:F301

b:70.9
occ:1.00
 F2 B:S6D301 0.0 70.9 1.0
C16 B:S6D301 1.3 65.1 1.0
F1 B:S6D301 2.1 63.7 1.0
F3 B:S6D301 2.2 68.2 1.0
C6 B:S6D301 2.4 55.1 1.0
N2 B:S6D301 2.8 49.0 1.0
CA B:GLY286 3.3 41.8 1.0
O B:HOH443 3.4 40.3 1.0
C7 B:S6D301 3.4 49.8 1.0
CA B:PRO246 3.5 45.1 1.0
CD B:PRO247 3.7 47.8 1.0
SG B:CYS289 3.8 51.1 1.0
O B:PHE245 3.9 49.6 1.0
N B:PRO246 3.9 45.6 1.0
CB B:CYS289 4.0 46.6 1.0
O B:GLY286 4.0 45.4 1.0
C5 B:S6D301 4.1 49.1 1.0
C B:PHE245 4.1 49.8 1.0
N B:GLY286 4.1 41.2 1.0
C B:GLY286 4.2 45.7 1.0
CB B:PRO246 4.2 47.1 1.0
N B:PRO247 4.5 47.2 1.0
C B:PRO246 4.5 49.0 1.0
O B:ALA285 4.5 42.1 1.0
C8 B:S6D301 4.6 50.0 1.0
C B:ALA285 4.6 42.5 1.0
N3 B:S6D301 4.8 50.8 1.0
CD B:PRO246 4.8 47.2 1.0
N B:PHE245 4.9 46.4 1.0
CB B:ALA244 5.0 43.5 1.0
CG B:PRO247 5.0 52.4 1.0

Fluorine binding site 6 out of 6 in 6w0z

Go back to Fluorine Binding Sites List in 6w0z
Fluorine binding site 6 out of 6 in the Structure of Khk in Complex with Compound 8 (2-[(1~{S},5~{R})-3-[2- [(2~{S})-2-Methylazetidin-1-Yl]-6-(Trifluoromethyl)Pyrimidin-4-Yl]-3- Azabicyclo[3.1.0]Hexan-6-Yl]Ethanoic Acid)


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 8 (2-[(1~{S},5~{R})-3-[2- [(2~{S})-2-Methylazetidin-1-Yl]-6-(Trifluoromethyl)Pyrimidin-4-Yl]-3- Azabicyclo[3.1.0]Hexan-6-Yl]Ethanoic Acid) within 5.0Å range:
probe atom residue distance (Å) B Occ
B:F301

b:68.2
occ:1.00
 F3 B:S6D301 0.0 68.2 1.0
C16 B:S6D301 1.3 65.1 1.0
F2 B:S6D301 2.2 70.9 1.0
F1 B:S6D301 2.2 63.7 1.0
C6 B:S6D301 2.4 55.1 1.0
C7 B:S6D301 2.8 49.8 1.0
N2 B:S6D301 3.6 49.0 1.0
OE1 B:GLU227 3.8 69.3 1.0
CD B:PRO247 4.1 47.8 1.0
SG B:CYS289 4.1 51.1 1.0
CA B:PRO246 4.1 45.1 1.0
CB B:PRO246 4.1 47.1 1.0
C8 B:S6D301 4.1 50.0 1.0
CB B:GLU227 4.2 49.5 1.0
CB B:CYS289 4.3 46.6 1.0
CG2 B:VAL250 4.4 58.0 1.0
C5 B:S6D301 4.6 49.1 1.0
CD B:GLU227 4.7 75.1 1.0
CA B:GLU227 4.8 47.1 1.0
N B:PRO246 4.9 45.6 1.0
N3 B:S6D301 4.9 50.8 1.0
CG B:GLU227 5.0 61.2 1.0

Reference:

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
Page generated: Sun Dec 13 13:26:24 2020

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