Fluorine in PDB 8j63: The Crystal Structure of Trka Kinase in Complex with 4^6-Methyl-N-(3- (4-Methyl-1H-Imidazol-1-Yl)-5-(Trifluoromethyl)Phenyl)-11-Oxo-5-Oxa- 10,14-Diaza-1(3,6)-Imidazo[1,2-B]Pyridazina-4(1,3)- Benzenacyclotetradecaphan-2-Yne-4^5-Carboxamide

Enzymatic activity of The Crystal Structure of Trka Kinase in Complex with 4^6-Methyl-N-(3- (4-Methyl-1H-Imidazol-1-Yl)-5-(Trifluoromethyl)Phenyl)-11-Oxo-5-Oxa- 10,14-Diaza-1(3,6)-Imidazo[1,2-B]Pyridazina-4(1,3)- Benzenacyclotetradecaphan-2-Yne-4^5-Carboxamide

All present enzymatic activity of The Crystal Structure of Trka Kinase in Complex with 4^6-Methyl-N-(3- (4-Methyl-1H-Imidazol-1-Yl)-5-(Trifluoromethyl)Phenyl)-11-Oxo-5-Oxa- 10,14-Diaza-1(3,6)-Imidazo[1,2-B]Pyridazina-4(1,3)- Benzenacyclotetradecaphan-2-Yne-4^5-Carboxamide:
2.7.10.1;

Protein crystallography data

The structure of The Crystal Structure of Trka Kinase in Complex with 4^6-Methyl-N-(3- (4-Methyl-1H-Imidazol-1-Yl)-5-(Trifluoromethyl)Phenyl)-11-Oxo-5-Oxa- 10,14-Diaza-1(3,6)-Imidazo[1,2-B]Pyridazina-4(1,3)- Benzenacyclotetradecaphan-2-Yne-4^5-Carboxamide, PDB code: 8j63 was solved by Z.M.Zhang, Y.J.Wang, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å) 25.41 / 3.00
Space group P 31 1 2
Cell size a, b, c (Å), α, β, γ (°) 52.125, 52.125, 228.168, 90, 90, 120
R / Rfree (%) 22.6 / 28.9

Fluorine Binding Sites:

The binding sites of Fluorine atom in the The Crystal Structure of Trka Kinase in Complex with 4^6-Methyl-N-(3- (4-Methyl-1H-Imidazol-1-Yl)-5-(Trifluoromethyl)Phenyl)-11-Oxo-5-Oxa- 10,14-Diaza-1(3,6)-Imidazo[1,2-B]Pyridazina-4(1,3)- Benzenacyclotetradecaphan-2-Yne-4^5-Carboxamide (pdb code 8j63). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 3 binding sites of Fluorine where determined in the The Crystal Structure of Trka Kinase in Complex with 4^6-Methyl-N-(3- (4-Methyl-1H-Imidazol-1-Yl)-5-(Trifluoromethyl)Phenyl)-11-Oxo-5-Oxa- 10,14-Diaza-1(3,6)-Imidazo[1,2-B]Pyridazina-4(1,3)- Benzenacyclotetradecaphan-2-Yne-4^5-Carboxamide, PDB code: 8j63:
Jump to Fluorine binding site number: 1; 2; 3;

Fluorine binding site 1 out of 3 in 8j63

Go back to Fluorine Binding Sites List in 8j63
Fluorine binding site 1 out of 3 in the The Crystal Structure of Trka Kinase in Complex with 4^6-Methyl-N-(3- (4-Methyl-1H-Imidazol-1-Yl)-5-(Trifluoromethyl)Phenyl)-11-Oxo-5-Oxa- 10,14-Diaza-1(3,6)-Imidazo[1,2-B]Pyridazina-4(1,3)- Benzenacyclotetradecaphan-2-Yne-4^5-Carboxamide


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of The Crystal Structure of Trka Kinase in Complex with 4^6-Methyl-N-(3- (4-Methyl-1H-Imidazol-1-Yl)-5-(Trifluoromethyl)Phenyl)-11-Oxo-5-Oxa- 10,14-Diaza-1(3,6)-Imidazo[1,2-B]Pyridazina-4(1,3)- Benzenacyclotetradecaphan-2-Yne-4^5-Carboxamide within 5.0Å range:
probe atom residue distance (Å) B Occ
A:F801

b:68.0
occ:1.00
 F46 A:A6X801 0.0 68.0 1.0
C45 A:A6X801 1.3 67.9 1.0
F48 A:A6X801 2.2 68.0 1.0
F47 A:A6X801 2.2 68.2 1.0
C32 A:A6X801 2.3 67.8 1.0
C31 A:A6X801 3.1 67.7 1.0
C33 A:A6X801 3.2 67.8 1.0
C A:GLY667 3.6 41.3 1.0
CA A:GLY667 3.6 42.1 1.0
NE2 A:HIS648 3.6 25.4 1.0
O A:GLY667 3.8 38.7 1.0
CD2 A:HIS648 4.0 26.7 1.0
N A:ASP668 4.0 47.9 1.0
N A:GLY667 4.1 39.5 1.0
CB A:ASP668 4.1 49.8 1.0
O A:ILE666 4.2 22.8 1.0
C A:ILE666 4.3 22.2 1.0
C30 A:A6X801 4.4 67.8 1.0
CG2 A:ILE666 4.4 23.4 1.0
C28 A:A6X801 4.5 68.0 1.0
CA A:ASP668 4.7 50.7 1.0
CE1 A:HIS648 4.7 25.8 1.0
CG2 A:ILE572 4.8 27.0 1.0
CE2 A:PHE646 4.8 33.2 1.0
CD1 A:LEU641 4.9 29.4 1.0
C29 A:A6X801 4.9 67.8 1.0

Fluorine binding site 2 out of 3 in 8j63

Go back to Fluorine Binding Sites List in 8j63
Fluorine binding site 2 out of 3 in the The Crystal Structure of Trka Kinase in Complex with 4^6-Methyl-N-(3- (4-Methyl-1H-Imidazol-1-Yl)-5-(Trifluoromethyl)Phenyl)-11-Oxo-5-Oxa- 10,14-Diaza-1(3,6)-Imidazo[1,2-B]Pyridazina-4(1,3)- Benzenacyclotetradecaphan-2-Yne-4^5-Carboxamide


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of The Crystal Structure of Trka Kinase in Complex with 4^6-Methyl-N-(3- (4-Methyl-1H-Imidazol-1-Yl)-5-(Trifluoromethyl)Phenyl)-11-Oxo-5-Oxa- 10,14-Diaza-1(3,6)-Imidazo[1,2-B]Pyridazina-4(1,3)- Benzenacyclotetradecaphan-2-Yne-4^5-Carboxamide within 5.0Å range:
probe atom residue distance (Å) B Occ
A:F801

b:68.2
occ:1.00
 F47 A:A6X801 0.0 68.2 1.0
C45 A:A6X801 1.3 67.9 1.0
F46 A:A6X801 2.2 68.0 1.0
F48 A:A6X801 2.2 68.0 1.0
C32 A:A6X801 2.3 67.8 1.0
C33 A:A6X801 2.7 67.8 1.0
CG2 A:ILE572 3.3 27.0 1.0
C31 A:A6X801 3.6 67.7 1.0
O A:ILE666 3.7 22.8 1.0
CA A:GLY667 3.9 42.1 1.0
CD2 A:LEU564 3.9 28.6 1.0
C28 A:A6X801 4.1 68.0 1.0
C A:ILE666 4.4 22.2 1.0
C A:GLY667 4.5 41.3 1.0
N A:GLY667 4.6 39.5 1.0
O27 A:A6X801 4.7 69.3 1.0
CD1 A:LEU567 4.7 42.9 1.0
N A:ASP668 4.7 47.9 1.0
C30 A:A6X801 4.7 67.8 1.0
CB A:ILE572 4.8 27.4 1.0
N A:VAL573 4.9 29.8 1.0
C29 A:A6X801 4.9 67.8 1.0

Fluorine binding site 3 out of 3 in 8j63

Go back to Fluorine Binding Sites List in 8j63
Fluorine binding site 3 out of 3 in the The Crystal Structure of Trka Kinase in Complex with 4^6-Methyl-N-(3- (4-Methyl-1H-Imidazol-1-Yl)-5-(Trifluoromethyl)Phenyl)-11-Oxo-5-Oxa- 10,14-Diaza-1(3,6)-Imidazo[1,2-B]Pyridazina-4(1,3)- Benzenacyclotetradecaphan-2-Yne-4^5-Carboxamide


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of The Crystal Structure of Trka Kinase in Complex with 4^6-Methyl-N-(3- (4-Methyl-1H-Imidazol-1-Yl)-5-(Trifluoromethyl)Phenyl)-11-Oxo-5-Oxa- 10,14-Diaza-1(3,6)-Imidazo[1,2-B]Pyridazina-4(1,3)- Benzenacyclotetradecaphan-2-Yne-4^5-Carboxamide within 5.0Å range:
probe atom residue distance (Å) B Occ
A:F801

b:68.0
occ:1.00
 F48 A:A6X801 0.0 68.0 1.0
C45 A:A6X801 1.3 67.9 1.0
F46 A:A6X801 2.2 68.0 1.0
F47 A:A6X801 2.2 68.2 1.0
C32 A:A6X801 2.3 67.8 1.0
C31 A:A6X801 2.7 67.7 1.0
CD1 A:LEU567 3.2 42.9 1.0
C33 A:A6X801 3.6 67.8 1.0
CE2 A:PHE646 4.1 33.2 1.0
C30 A:A6X801 4.1 67.8 1.0
CZ A:PHE646 4.3 34.5 1.0
CD2 A:LEU564 4.4 28.6 1.0
CG A:LEU567 4.4 43.1 1.0
CG2 A:ILE572 4.5 27.0 1.0
CB A:LEU567 4.7 39.6 1.0
C28 A:A6X801 4.7 68.0 1.0
CD2 A:PHE646 4.8 34.5 1.0
CD2 A:LEU641 4.9 32.2 1.0
C29 A:A6X801 4.9 67.8 1.0

Reference:

Z.Wang, J.Wang, Y.Wang, S.Xiang, H.Zhou, S.Song, X.Song, Z.Tu, Y.Zhou, K.Ding, Z.M.Zhang, Z.Zhang, X.Lu. Structure-Based Optimization of the Third Generation Type II Macrocycle Trk Inhibitors with Improved Activity Against Solvent-Front, Xdfg, and Gatekeeper Mutations. J.Med.Chem. 2023.
ISSN: ISSN 0022-2623
PubMed: 37676745
DOI: 10.1021/ACS.JMEDCHEM.3C00899
Page generated: Fri Aug 2 20:53:30 2024

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