Fluorine in PDB 5t18: Crystal Structure of Bruton Agammabulinemia Tyrosine Kinase Complexed with Bms-986142 Aka (2S)-6-Fluoro-5-[3-(8-Fluoro-1-Methyl-2,4-Dioxo- 1,2,3,4-Tetrahydroquinazolin-3-Yl)-2-Methylphenyl]-2-(2- Hydroxypropan-2-Yl)-2,3,4,9-Tetrahydro-1H-Carbazole-8-Carboxamide

Enzymatic activity of Crystal Structure of Bruton Agammabulinemia Tyrosine Kinase Complexed with Bms-986142 Aka (2S)-6-Fluoro-5-[3-(8-Fluoro-1-Methyl-2,4-Dioxo- 1,2,3,4-Tetrahydroquinazolin-3-Yl)-2-Methylphenyl]-2-(2- Hydroxypropan-2-Yl)-2,3,4,9-Tetrahydro-1H-Carbazole-8-Carboxamide

All present enzymatic activity of Crystal Structure of Bruton Agammabulinemia Tyrosine Kinase Complexed with Bms-986142 Aka (2S)-6-Fluoro-5-[3-(8-Fluoro-1-Methyl-2,4-Dioxo- 1,2,3,4-Tetrahydroquinazolin-3-Yl)-2-Methylphenyl]-2-(2- Hydroxypropan-2-Yl)-2,3,4,9-Tetrahydro-1H-Carbazole-8-Carboxamide:
2.7.10.2;

Protein crystallography data

The structure of Crystal Structure of Bruton Agammabulinemia Tyrosine Kinase Complexed with Bms-986142 Aka (2S)-6-Fluoro-5-[3-(8-Fluoro-1-Methyl-2,4-Dioxo- 1,2,3,4-Tetrahydroquinazolin-3-Yl)-2-Methylphenyl]-2-(2- Hydroxypropan-2-Yl)-2,3,4,9-Tetrahydro-1H-Carbazole-8-Carboxamide, PDB code: 5t18 was solved by J.K.Muckelbauer, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å) 30.00 / 1.50
Space group P 21 21 21
Cell size a, b, c (Å), α, β, γ (°) 46.604, 69.759, 88.955, 90.00, 90.00, 90.00
R / Rfree (%) 20.3 / 22.3

Fluorine Binding Sites:

The binding sites of Fluorine atom in the Crystal Structure of Bruton Agammabulinemia Tyrosine Kinase Complexed with Bms-986142 Aka (2S)-6-Fluoro-5-[3-(8-Fluoro-1-Methyl-2,4-Dioxo- 1,2,3,4-Tetrahydroquinazolin-3-Yl)-2-Methylphenyl]-2-(2- Hydroxypropan-2-Yl)-2,3,4,9-Tetrahydro-1H-Carbazole-8-Carboxamide (pdb code 5t18). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 2 binding sites of Fluorine where determined in the Crystal Structure of Bruton Agammabulinemia Tyrosine Kinase Complexed with Bms-986142 Aka (2S)-6-Fluoro-5-[3-(8-Fluoro-1-Methyl-2,4-Dioxo- 1,2,3,4-Tetrahydroquinazolin-3-Yl)-2-Methylphenyl]-2-(2- Hydroxypropan-2-Yl)-2,3,4,9-Tetrahydro-1H-Carbazole-8-Carboxamide, PDB code: 5t18:
Jump to Fluorine binding site number: 1; 2;

Fluorine binding site 1 out of 2 in 5t18

Go back to Fluorine Binding Sites List in 5t18
Fluorine binding site 1 out of 2 in the Crystal Structure of Bruton Agammabulinemia Tyrosine Kinase Complexed with Bms-986142 Aka (2S)-6-Fluoro-5-[3-(8-Fluoro-1-Methyl-2,4-Dioxo- 1,2,3,4-Tetrahydroquinazolin-3-Yl)-2-Methylphenyl]-2-(2- Hydroxypropan-2-Yl)-2,3,4,9-Tetrahydro-1H-Carbazole-8-Carboxamide


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 Bruton Agammabulinemia Tyrosine Kinase Complexed with Bms-986142 Aka (2S)-6-Fluoro-5-[3-(8-Fluoro-1-Methyl-2,4-Dioxo- 1,2,3,4-Tetrahydroquinazolin-3-Yl)-2-Methylphenyl]-2-(2- Hydroxypropan-2-Yl)-2,3,4,9-Tetrahydro-1H-Carbazole-8-Carboxamide within 5.0Å range:
probe atom residue distance (Å) B Occ
A:F701

b:27.9
occ:1.00
 F35 A:73T701 0.0 27.9 1.0
C31 A:73T701 1.3 20.8 1.0
C32 A:73T701 2.3 23.1 1.0
C28 A:73T701 2.4 16.9 1.0
H70 A:73T701 2.4 24.1 1.0
H72 A:73T701 2.5 25.4 1.0
H58 A:73T701 2.5 24.3 1.0
C42 A:73T701 2.7 23.6 1.0
HB2 A:ARG525 2.7 20.1 1.0
N27 A:73T701 2.9 18.8 1.0
HD2 A:ARG525 3.1 23.4 1.0
O A:HOH947 3.2 43.2 1.0
HD3 A:ARG525 3.4 23.7 1.0
HB3 A:ARG525 3.5 18.9 1.0
CB A:ARG525 3.5 19.7 1.0
C33 A:73T701 3.6 22.0 1.0
CD A:ARG525 3.6 23.4 1.0
C29 A:73T701 3.7 18.3 1.0
H71 A:73T701 3.7 23.6 1.0
CG A:ARG525 4.1 21.9 1.0
C34 A:73T701 4.1 19.9 1.0
C26 A:73T701 4.3 17.8 1.0
HD23 A:LEU483 4.4 23.6 1.0
H59 A:73T701 4.4 23.0 1.0
HG3 A:ARG525 4.5 22.4 1.0
O A:HOH835 4.6 31.4 1.0
HA A:ARG525 4.7 15.4 1.0
CA A:ARG525 4.8 18.5 1.0
O A:HOH940 4.8 32.9 1.0
O A:HOH926 4.8 25.1 1.0
HD22 A:LEU483 4.9 21.7 1.0
C30 A:73T701 4.9 17.1 1.0
NE A:ARG525 5.0 28.6 1.0

Fluorine binding site 2 out of 2 in 5t18

Go back to Fluorine Binding Sites List in 5t18
Fluorine binding site 2 out of 2 in the Crystal Structure of Bruton Agammabulinemia Tyrosine Kinase Complexed with Bms-986142 Aka (2S)-6-Fluoro-5-[3-(8-Fluoro-1-Methyl-2,4-Dioxo- 1,2,3,4-Tetrahydroquinazolin-3-Yl)-2-Methylphenyl]-2-(2- Hydroxypropan-2-Yl)-2,3,4,9-Tetrahydro-1H-Carbazole-8-Carboxamide


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 Bruton Agammabulinemia Tyrosine Kinase Complexed with Bms-986142 Aka (2S)-6-Fluoro-5-[3-(8-Fluoro-1-Methyl-2,4-Dioxo- 1,2,3,4-Tetrahydroquinazolin-3-Yl)-2-Methylphenyl]-2-(2- Hydroxypropan-2-Yl)-2,3,4,9-Tetrahydro-1H-Carbazole-8-Carboxamide within 5.0Å range:
probe atom residue distance (Å) B Occ
A:F701

b:18.7
occ:1.00
 F38 A:73T701 0.0 18.7 1.0
C4 A:73T701 1.4 16.3 1.0
C5 A:73T701 2.3 15.9 1.0
C3 A:73T701 2.4 15.7 1.0
HE2 A:LYS430 2.5 34.6 1.0
H43 A:73T701 2.5 13.9 1.0
C18 A:73T701 2.8 16.0 1.0
O A:HOH836 2.8 30.3 1.0
HZ3 A:LYS430 3.0 44.1 1.0
HG21 A:VAL416 3.1 18.0 1.0
HG11 A:VAL416 3.2 16.1 1.0
H69 A:73T701 3.2 16.3 1.0
O A:HOH858 3.3 31.0 1.0
CE A:LYS430 3.3 34.1 1.0
C23 A:73T701 3.3 15.6 1.0
NZ A:LYS430 3.4 44.2 1.0
HZ2 A:LYS430 3.5 44.5 1.0
H67 A:73T701 3.5 17.9 1.0
C41 A:73T701 3.5 16.6 1.0
C19 A:73T701 3.5 17.2 1.0
C6 A:73T701 3.6 14.1 1.0
C2 A:73T701 3.6 14.9 1.0
H54 A:73T701 3.7 16.3 1.0
O A:HOH871 3.8 32.7 1.0
HE3 A:LYS430 3.8 34.2 1.0
C1 A:73T701 4.1 14.4 1.0
HD21 A:LEU528 4.1 23.2 1.0
CG2 A:VAL416 4.2 18.0 1.0
CG1 A:VAL416 4.2 16.9 1.0
O A:HOH912 4.2 35.6 1.0
HG2 A:LYS430 4.4 26.8 1.0
C22 A:73T701 4.4 16.1 1.0
HZ1 A:LYS430 4.4 44.0 1.0
HD11 A:LEU528 4.5 16.5 1.0
HG13 A:VAL416 4.5 11.7 1.0
CD A:LYS430 4.6 34.3 1.0
C20 A:73T701 4.6 18.6 1.0
O A:HOH900 4.6 20.2 1.0
H68 A:73T701 4.6 17.9 1.0
H52 A:73T701 4.6 14.9 1.0
HG22 A:VAL416 4.6 17.6 1.0
HD3 A:LYS430 4.7 34.9 1.0
CB A:VAL416 4.7 17.8 1.0
HD13 A:LEU528 4.8 16.2 1.0
HG23 A:VAL416 4.8 18.4 1.0
HB A:VAL416 4.8 14.2 1.0
C15 A:73T701 4.8 13.3 1.0
HG12 A:VAL416 4.9 14.9 1.0
C21 A:73T701 4.9 15.9 1.0
C9 A:73T701 4.9 15.9 1.0
CG A:LYS430 5.0 25.5 1.0

Reference:

S.H.Watterson, G.V.De Lucca, Q.Shi, C.M.Langevine, Q.Liu, D.G.Batt, M.Beaudoin Bertrand, H.Gong, J.Dai, S.Yip, P.Li, D.Sun, D.R.Wu, C.Wang, Y.Zhang, S.C.Traeger, M.A.Pattoli, S.Skala, L.Cheng, M.T.Obermeier, R.Vickery, L.N.Discenza, C.J.D'arienzo, Y.Zhang, E.Heimrich, K.M.Gillooly, T.L.Taylor, C.Pulicicchio, K.W.Mcintyre, M.A.Galella, A.J.Tebben, J.K.Muckelbauer, C.Chang, R.Rampulla, A.Mathur, L.Salter-Cid, J.C.Barrish, P.H.Carter, A.Fura, J.R.Burke, J.A.Tino. Discovery of 6-Fluoro-5-(R)-(3-(S)-(8-Fluoro-1-Methyl-2,4-Dioxo-1, 2-Dihydroquinazolin-3(4H)-Yl)-2-Methylphenyl)-2-(S) -(2-Hydroxypropan-2-Yl)-2,3,4, 9-Tetrahydro-1H-Carbazole-8-Carboxamide (Bms-986142): A Reversible Inhibitor of Bruton'S Tyrosine Kinase (Btk) Conformationally Constrained By Two Locked Atropisomers. J. Med. Chem. V. 59 9173 2016.
ISSN: ISSN 1520-4804
PubMed: 27583770
DOI: 10.1021/ACS.JMEDCHEM.6B01088
Page generated: Sun Dec 13 12:37:39 2020

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