Fluorine in PDB 8fln: Crystal Structure of Btk C481S Kinase Domain in Complex with Pirtobrutinib

All present enzymatic activity of Crystal Structure of Btk C481S Kinase Domain in Complex with Pirtobrutinib:
2.7.10.2;

The structure of Crystal Structure of Btk C481S Kinase Domain in Complex with Pirtobrutinib, PDB code: 8fln was solved by E.P.Cedervall, C.K.Allerston, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	19.40 / 1.33
Space group	P 21 21 21
Cell size a, b, c (Å), α, β, γ (°)	41.595, 67.036, 90.675, 90, 90, 90
R / Rfree (%)	19.3 / 19.9

The binding sites of Fluorine atom in the Crystal Structure of Btk C481S Kinase Domain in Complex with Pirtobrutinib (pdb code 8fln). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 4 binding sites of Fluorine where determined in the Crystal Structure of Btk C481S Kinase Domain in Complex with Pirtobrutinib, PDB code: 8fln:
Jump to Fluorine binding site number: 1; 2; 3; 4;

Fluorine binding site 1 out of 4 in the Crystal Structure of Btk C481S Kinase Domain in Complex with Pirtobrutinib


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 Btk C481S Kinase Domain in Complex with Pirtobrutinib within 5.0Å range: probe atom residue distance (Å) B Occ A:F701 b:23.9 occ:1.00 F16 A:Y7W701 0.0 23.9 1.0 C15 A:Y7W701 1.4 21.8 1.0 C17 A:Y7W701 2.3 19.3 1.0 C14 A:Y7W701 2.3 20.6 1.0 CE A:MET449 2.9 33.3 0.6 SD A:MET449 3.1 35.0 0.6 CB A:LEU542 3.4 21.4 1.0 O A:PHE540 3.4 19.4 1.0 CE A:MET449 3.4 31.3 0.4 CA A:LEU542 3.5 21.3 1.0 CE1 A:PHE442 3.5 29.4 1.0 N A:LEU542 3.6 20.4 1.0 C18 A:Y7W701 3.6 18.3 1.0 C13 A:Y7W701 3.6 19.9 1.0 CD1 A:LEU542 3.8 24.2 1.0 C19 A:Y7W701 4.1 19.5 1.0 CZ A:PHE442 4.1 29.6 1.0 CG A:LEU542 4.1 22.4 1.0 C A:GLY541 4.2 20.8 1.0 C A:PHE540 4.2 18.8 1.0 CG A:MET449 4.3 31.0 0.6 C A:ASP539 4.3 19.4 1.0 N A:PHE540 4.5 18.5 1.0 O A:ASP539 4.5 19.8 1.0 CA A:ASP539 4.5 19.9 1.0 CD1 A:PHE442 4.6 29.4 1.0 CG A:MET449 4.6 25.7 0.4 O A:GLY541 4.6 22.5 1.0 CD2 A:LEU542 4.7 23.3 1.0 C12 A:Y7W701 4.8 21.6 1.0 N A:GLY541 4.8 19.0 1.0 CA A:GLY541 4.8 20.2 1.0 SD A:MET449 4.9 31.2 0.4 O22 A:Y7W701 4.9 24.2 1.0 C A:LEU542 4.9 22.3 1.0 CA A:PHE540 5.0 18.5 1.0

Fluorine binding site 2 out of 4 in the Crystal Structure of Btk C481S Kinase Domain in Complex with Pirtobrutinib


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 Btk C481S Kinase Domain in Complex with Pirtobrutinib within 5.0Å range: probe atom residue distance (Å) B Occ A:F701 b:22.5 occ:1.00 F30 A:Y7W701 0.0 22.5 1.0 C29 A:Y7W701 1.3 21.1 1.0 F32 A:Y7W701 2.1 22.7 1.0 F31 A:Y7W701 2.1 22.2 1.0 C27 A:Y7W701 2.3 19.0 1.0 N26 A:Y7W701 2.7 17.7 1.0 CB A:LEU408 3.1 22.4 1.0 C33 A:Y7W701 3.3 17.5 1.0 N25 A:Y7W701 3.4 17.3 1.0 CB A:VAL416 3.5 20.1 1.0 O A:HOH917 3.5 27.7 1.0 CG1 A:VAL416 3.6 21.4 1.0 N34 A:Y7W701 3.7 18.6 1.0 C28 A:Y7W701 3.7 19.6 1.0 C A:LEU408 3.7 25.3 1.0 O A:LEU408 3.9 24.6 1.0 CG2 A:VAL416 4.0 20.7 1.0 N A:GLY409 4.0 25.3 1.0 CD1 A:LEU408 4.0 23.0 1.0 CA A:LEU408 4.1 22.8 1.0 CG A:LEU408 4.2 23.0 1.0 C4 A:Y7W701 4.2 16.7 1.0 C5 A:Y7W701 4.2 17.1 1.0 CA A:GLY409 4.3 26.4 1.0 C A:GLY409 4.8 25.9 1.0 CA A:VAL416 4.8 19.4 1.0 O A:VAL416 4.8 20.4 1.0 O A:GLY409 4.9 25.3 1.0 O A:HOH888 5.0 22.4 1.0

Fluorine binding site 3 out of 4 in the Crystal Structure of Btk C481S Kinase Domain in Complex with Pirtobrutinib


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Crystal Structure of Btk C481S Kinase Domain in Complex with Pirtobrutinib within 5.0Å range: probe atom residue distance (Å) B Occ A:F701 b:22.2 occ:1.00 F31 A:Y7W701 0.0 22.2 1.0 C29 A:Y7W701 1.3 21.1 1.0 F30 A:Y7W701 2.1 22.5 1.0 F32 A:Y7W701 2.2 22.7 1.0 C27 A:Y7W701 2.3 19.0 1.0 C28 A:Y7W701 3.0 19.6 1.0 O A:LEU408 3.6 24.6 1.0 N26 A:Y7W701 3.6 17.7 1.0 O A:HOH917 3.7 27.7 1.0 CA A:GLY409 3.9 26.4 1.0 C A:LEU408 4.0 25.3 1.0 N A:GLY409 4.2 25.3 1.0 N25 A:Y7W701 4.4 17.3 1.0 CB A:LEU408 4.5 22.4 1.0 C A:GLY409 4.5 25.9 1.0 C33 A:Y7W701 4.5 17.5 1.0 O A:HOH950 4.6 37.8 1.0 N34 A:Y7W701 4.8 18.6 1.0 O A:HOH841 4.9 37.4 1.0 N A:THR410 4.9 27.6 1.0 CA A:LEU408 5.0 22.8 1.0

Fluorine binding site 4 out of 4 in the Crystal Structure of Btk C481S Kinase Domain in Complex with Pirtobrutinib


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 4 of Crystal Structure of Btk C481S Kinase Domain in Complex with Pirtobrutinib within 5.0Å range: probe atom residue distance (Å) B Occ A:F701 b:22.7 occ:1.00 F32 A:Y7W701 0.0 22.7 1.0 C29 A:Y7W701 1.3 21.1 1.0 F30 A:Y7W701 2.1 22.5 1.0 F31 A:Y7W701 2.2 22.2 1.0 C27 A:Y7W701 2.4 19.0 1.0 C28 A:Y7W701 2.9 19.6 1.0 N26 A:Y7W701 2.9 17.7 1.0 N25 A:Y7W701 3.0 17.3 1.0 O A:HOH950 3.2 37.8 1.0 O A:HOH888 3.2 22.4 1.0 CG2 A:VAL416 3.4 20.7 1.0 CB A:VAL416 3.7 20.1 1.0 C33 A:Y7W701 4.1 17.5 1.0 C5 A:Y7W701 4.2 17.1 1.0 CG1 A:VAL416 4.3 21.4 1.0 C A:GLY409 4.4 25.9 1.0 CA A:GLY409 4.5 26.4 1.0 O A:GLY409 4.7 25.3 1.0 N A:THR410 4.8 27.6 1.0 N A:GLY409 4.8 25.3 1.0 C4 A:Y7W701 4.8 16.7 1.0 N34 A:Y7W701 4.9 18.6 1.0

E.B.Gomez, K.Ebata, H.S.Randeria, M.S.Rosendahl, E.P.Cedervall, T.H.Morales, L.M.Hanson, N.E.Brown, X.Gong, J.R.Stephens, W.Wu, I.Lippincott, K.S.Ku, R.A.Walgren, P.B.Abada, J.A.Ballard, C.K.Allerston, B.J.Brandhuber. Pirtobrutinib Preclinical Characterization: A Highly Selective, Non-Covalent (Reversible) Btk Inhibitor. Blood 2023.
ISSN: ESSN 1528-0020
PubMed: 36796019
DOI: 10.1182/BLOOD.2022018674