Fluorine in PDB 6xe4: Btk Fluorocyclopropyl Amide Inhibitor, Compound 25

All present enzymatic activity of Btk Fluorocyclopropyl Amide Inhibitor, Compound 25:
2.7.10.2;

The structure of Btk Fluorocyclopropyl Amide Inhibitor, Compound 25, PDB code: 6xe4 was solved by J.R.Kiefer, J.J.Crawford, W.Lee, C.Eigenbrot, C.Yu, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	33.28 / 1.60
Space group	P 61
Cell size a, b, c (Å), α, β, γ (°)	108.280, 108.280, 42.202, 90.00, 90.00, 120.00
R / Rfree (%)	15.8 / 18

The binding sites of Fluorine atom in the Btk Fluorocyclopropyl Amide Inhibitor, Compound 25 (pdb code 6xe4). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 2 binding sites of Fluorine where determined in the Btk Fluorocyclopropyl Amide Inhibitor, Compound 25, PDB code: 6xe4:
Jump to Fluorine binding site number: 1; 2;

Fluorine binding site 1 out of 2 in the Btk Fluorocyclopropyl Amide Inhibitor, Compound 25


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Btk Fluorocyclopropyl Amide Inhibitor, Compound 25 within 5.0Å range: probe atom residue distance (Å) B Occ A:F701 b:19.9 occ:1.00 F16 A:V1G701 0.0 19.9 1.0 C14 A:V1G701 1.3 15.9 1.0 C15 A:V1G701 2.4 15.4 1.0 C13 A:V1G701 2.4 12.7 1.0 HZ2 A:LYS430 2.5 20.1 1.0 HD2 A:PHE413 2.5 22.7 1.0 O12 A:V1G701 2.7 14.2 1.0 HD3 A:LYS430 2.8 18.5 1.0 C11 A:V1G701 2.9 14.9 1.0 HE3 A:LYS430 2.9 20.0 1.0 NZ A:LYS430 3.2 16.8 1.0 CD2 A:PHE413 3.3 18.9 1.0 CE A:LYS430 3.3 16.6 1.0 HE2 A:PHE413 3.4 22.2 1.0 HD13 A:LEU542 3.5 23.6 1.0 CD A:LYS430 3.5 15.4 1.0 O A:HOH942 3.5 18.3 1.0 HZ1 A:LYS430 3.6 20.1 1.0 C5 A:V1G701 3.6 13.9 1.0 C7 A:V1G701 3.6 14.2 1.0 CE2 A:PHE413 3.8 18.5 1.0 OD1 A:ASP539 3.8 20.4 1.0 CG A:ASP539 3.9 21.2 1.0 HZ3 A:LYS430 3.9 20.1 1.0 HD2 A:LYS430 3.9 18.5 1.0 OD2 A:ASP539 3.9 18.7 1.0 HD12 A:LEU542 3.9 23.6 1.0 HB2 A:PHE413 4.0 21.6 1.0 H A:PHE413 4.1 20.3 1.0 C6 A:V1G701 4.1 15.2 1.0 CD1 A:LEU542 4.1 19.7 1.0 HB3 A:GLN412 4.2 24.5 1.0 N10 A:V1G701 4.2 14.9 1.0 HB3 A:ASP539 4.3 16.1 1.0 HE2 A:LYS430 4.3 20.0 1.0 H A:GLN412 4.3 20.9 1.0 CG A:PHE413 4.4 16.4 1.0 HD11 A:LEU542 4.6 23.6 1.0 HG2 A:LYS430 4.6 20.7 1.0 CB A:ASP539 4.7 13.4 1.0 CG A:LYS430 4.7 17.3 1.0 CB A:PHE413 4.7 18.0 1.0 O41 A:V1G701 4.8 16.6 1.0 N A:PHE413 4.8 16.9 1.0 HA3 A:GLY411 4.8 22.2 1.0 C8 A:V1G701 4.8 20.0 1.0 HB3 A:LEU542 4.9 17.2 1.0 C2 A:V1G701 4.9 16.3 1.0 C3 A:V1G701 4.9 19.2 1.0 N A:GLN412 4.9 17.4 1.0

Fluorine binding site 2 out of 2 in the Btk Fluorocyclopropyl Amide Inhibitor, Compound 25


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Btk Fluorocyclopropyl Amide Inhibitor, Compound 25 within 5.0Å range: probe atom residue distance (Å) B Occ A:F701 b:18.4 occ:1.00 F39 A:V1G701 0.0 18.4 1.0 C37 A:V1G701 1.4 14.5 1.0 H38 A:V1G701 2.1 17.4 1.0 C34 A:V1G701 2.5 12.1 1.0 C36 A:V1G701 2.5 13.9 1.0 HA3 A:GLY480 2.5 15.5 1.0 O33 A:V1G701 2.8 15.7 1.0 C32 A:V1G701 2.9 13.1 1.0 CA A:GLY480 3.3 12.9 1.0 HA2 A:GLY480 3.3 15.5 1.0 O A:HOH981 3.4 17.2 0.5 H35 A:V1G701 3.4 14.6 1.0 O A:HOH959 3.5 20.1 0.6 O A:HOH959 3.6 25.5 0.5 O A:HOH903 3.6 26.9 1.0 N A:GLY480 3.8 12.0 1.0 O A:HOH1066 4.0 49.1 1.0 N31 A:V1G701 4.1 11.1 1.0 H A:CYS481 4.1 13.9 0.6 H A:CYS481 4.1 13.9 0.4 H A:GLY480 4.2 14.4 1.0 C A:ASN479 4.2 15.6 1.0 O A:ASN479 4.3 13.8 1.0 O A:ALA478 4.5 14.5 1.0 C A:GLY480 4.5 11.9 1.0 O A:HOH854 4.6 20.2 1.0 N A:CYS481 4.7 11.6 1.0 HD22 A:LEU408 4.8 22.7 1.0 HA A:ASN479 4.8 16.6 1.0

J.J.Crawford, W.Lee, A.R.Johnson, K.J.Delatorre, J.Chen, C.Eigenbrot, J.Heidmann, S.Kakiuchi-Kiyota, A.Katewa, J.R.Kiefer, L.Liu, J.W.Lubach, D.Misner, H.Purkey, K.Reif, J.Vogt, H.Wong, C.Yu, W.B.Young. Stereochemical Differences in Fluorocyclopropyl Amides Enable Tuning of Btk Inhibition and Off-Target Activity. Acs Med.Chem.Lett. V. 11 1588 2020.
ISSN: ISSN 1948-5875
PubMed: 32832028
DOI: 10.1021/ACSMEDCHEMLETT.0C00249