Fluorine in PDB 7v18: Factor Xia in Complex with Compound 3F

All present enzymatic activity of Factor Xia in Complex with Compound 3F:
3.4.21.27;

The structure of Factor Xia in Complex with Compound 3F, PDB code: 7v18 was solved by P.L.Shaffer, C.M.Milligan, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	35.42 / 1.73
Space group	P 21 21 21
Cell size a, b, c (Å), α, β, γ (°)	58.5, 59.79, 66.63, 90, 90, 90
R / Rfree (%)	17.1 / 20.7

The structure of Factor Xia in Complex with Compound 3F also contains other interesting chemical elements:

Chlorine

(Cl)

2 atoms

The binding sites of Fluorine atom in the Factor Xia in Complex with Compound 3F (pdb code 7v18). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 3 binding sites of Fluorine where determined in the Factor Xia in Complex with Compound 3F, PDB code: 7v18:
Jump to Fluorine binding site number: 1; 2; 3;

Fluorine binding site 1 out of 3 in the Factor Xia in Complex with Compound 3F


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Factor Xia in Complex with Compound 3F within 5.0Å range: probe atom residue distance (Å) B Occ A:F702 b:34.5 occ:1.00 F29 A:OTX702 0.0 34.5 1.0 C28 A:OTX702 1.3 30.3 1.0 C27 A:OTX702 2.4 30.5 1.0 C30 A:OTX702 2.4 35.8 1.0 C23 A:OTX702 2.7 31.1 1.0 CL31 A:OTX702 2.9 34.1 1.0 CG2 A:THR593 3.1 26.7 1.0 C24 A:OTX702 3.1 29.5 1.0 C A:SER594 3.3 31.2 1.0 N A:TRP595 3.4 27.4 1.0 O A:SER594 3.5 33.5 1.0 N A:SER594 3.5 25.1 1.0 C34 A:OTX702 3.6 35.2 1.0 C32 A:OTX702 3.6 37.6 1.0 C22 A:OTX702 3.7 35.7 1.0 CA A:TRP595 3.7 27.0 1.0 C A:THR593 3.9 27.9 1.0 CA A:SER594 3.9 28.5 1.0 C33 A:OTX702 4.1 30.8 1.0 N25 A:OTX702 4.1 33.9 1.0 CB A:SER575 4.1 30.8 1.0 C A:TRP595 4.2 32.5 1.0 CB A:THR593 4.3 25.3 1.0 O A:THR593 4.4 27.0 1.0 CA A:SER575 4.4 27.4 1.0 O A:TRP595 4.4 32.1 1.0 CB A:ALA570 4.5 36.1 1.0 CA A:THR593 4.5 24.9 1.0 C21 A:OTX702 4.6 30.4 1.0 N A:SER575 4.7 29.9 1.0 C20 A:OTX702 4.8 32.5 1.0 N35 A:OTX702 4.8 40.1 1.0 O26 A:OTX702 4.8 39.5 1.0 N A:GLY596 4.9 36.4 1.0 O A:VAL607 5.0 32.7 1.0

Fluorine binding site 2 out of 3 in the Factor Xia in Complex with Compound 3F


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Factor Xia in Complex with Compound 3F within 5.0Å range: probe atom residue distance (Å) B Occ A:F702 b:37.3 occ:1.00 F18 A:OTX702 0.0 37.3 1.0 C17 A:OTX702 1.4 32.6 1.0 F19 A:OTX702 2.2 38.2 1.0 O16 A:OTX702 2.2 31.6 1.0 C15 A:OTX702 2.6 32.9 1.0 C11 A:OTX702 3.4 27.8 1.0 C1 A:OTX702 3.6 36.8 1.0 O A:LEU415 3.7 29.6 1.0 CD1 A:LEU415 3.8 33.6 1.0 N10 A:OTX702 3.8 34.1 1.0 C7 A:OTX702 3.9 33.7 1.0 C14 A:OTX702 4.0 32.5 1.0 C12 A:OTX702 4.2 33.8 1.0 O A:HOH839 4.3 32.4 1.0 N2 A:OTX702 4.4 36.3 1.0 C6 A:OTX702 4.5 37.4 1.0 N9 A:OTX702 4.5 34.2 1.0 C8 A:OTX702 4.5 35.3 1.0 C A:LEU415 4.7 29.6 1.0 CG A:LEU415 4.8 34.1 1.0 SG A:CYS416 4.9 33.3 1.0 O A:HOH801 4.9 35.7 1.0 NH1 A:ARG413 5.0 69.2 1.0

Fluorine binding site 3 out of 3 in the Factor Xia in Complex with Compound 3F


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Factor Xia in Complex with Compound 3F within 5.0Å range: probe atom residue distance (Å) B Occ A:F702 b:38.2 occ:1.00 F19 A:OTX702 0.0 38.2 1.0 C17 A:OTX702 1.4 32.6 1.0 F18 A:OTX702 2.2 37.3 1.0 O16 A:OTX702 2.3 31.6 1.0 C15 A:OTX702 2.8 32.9 1.0 O A:CYS432 3.6 32.3 1.0 CA A:CYS432 3.6 25.8 1.0 O A:HOH801 3.6 35.7 1.0 O A:HIS431 3.7 32.0 1.0 CD1 A:LEU415 3.7 33.6 1.0 O A:HOH819 3.8 38.1 1.0 C A:CYS432 3.9 30.2 1.0 C14 A:OTX702 4.2 32.5 1.0 CD2 A:HIS431 4.3 29.7 1.0 C A:HIS431 4.3 29.7 1.0 SG A:CYS416 4.3 33.3 1.0 N A:CYS432 4.3 26.6 1.0 CG A:LEU415 4.5 34.1 1.0 O A:LEU415 4.5 29.6 1.0 CB A:CYS432 4.6 24.6 1.0 C12 A:OTX702 4.9 33.8 1.0

G.Xu, Z.Liu, X.Wang, T.Lu, R.L.Desjarlais, T.Thieu, J.Zhang, Z.H.Devine, F.Du, Q.Li, C.M.Milligan, P.Shaffer, P.E.Cedervall, J.C.Spurlino, C.F.Stratton, B.Pietrak, L.M.Szewczuk, V.Wong, R.A.Steele, W.Bruinzeel, M.Chintala, J.Silva, M.D.Gaul, M.J.Macielag, R.Nargund. Discovery of Potent and Orally Bioavailable Pyridine N-Oxide-Based Factor Xia Inhibitors Through Exploiting Nonclassical Interactions. J.Med.Chem. V. 65 10419 2022.
ISSN: ISSN 0022-2623
PubMed: 35862732
DOI: 10.1021/ACS.JMEDCHEM.2C00442