Fluorine in PDB 2xbv: Factor Xa in Complex with A Pyrrolidine-3,4-Dicarboxylic Acid Inhibitor

All present enzymatic activity of Factor Xa in Complex with A Pyrrolidine-3,4-Dicarboxylic Acid Inhibitor:
3.4.21.6;

The structure of Factor Xa in Complex with A Pyrrolidine-3,4-Dicarboxylic Acid Inhibitor, PDB code: 2xbv was solved by D.W.Banner, J.Benz, D.Schlatter, L.Anselm, W.Haap, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	19.52 / 1.66
Space group	P 43 21 2
Cell size a, b, c (Å), α, β, γ (°)	105.940, 105.940, 50.180, 90.00, 90.00, 90.00
R / Rfree (%)	19.2 / 22.44

The structure of Factor Xa in Complex with A Pyrrolidine-3,4-Dicarboxylic Acid Inhibitor also contains other interesting chemical elements:

Calcium	(Ca)	1 atom
Chlorine	(Cl)	1 atom
Sodium	(Na)	1 atom

The binding sites of Fluorine atom in the Factor Xa in Complex with A Pyrrolidine-3,4-Dicarboxylic Acid Inhibitor (pdb code 2xbv). 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 Xa in Complex with A Pyrrolidine-3,4-Dicarboxylic Acid Inhibitor, PDB code: 2xbv:
Jump to Fluorine binding site number: 1; 2; 3;

Fluorine binding site 1 out of 3 in the Factor Xa in Complex with A Pyrrolidine-3,4-Dicarboxylic Acid Inhibitor


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Factor Xa in Complex with A Pyrrolidine-3,4-Dicarboxylic Acid Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ A:F1245 b:22.0 occ:1.00 F32 A:XBV1245 0.0 22.0 1.0 C24 A:XBV1245 1.3 15.9 1.0 C19 A:XBV1245 2.4 14.9 1.0 C22 A:XBV1245 2.4 18.0 1.0 N8 A:XBV1245 2.6 22.2 1.0 O A:HOH2236 2.8 40.1 1.0 O A:HOH2119 2.9 33.4 1.0 CE2 A:TYR99 3.4 18.8 1.0 OH A:TYR99 3.4 22.2 1.0 CZ A:TYR99 3.4 22.6 1.0 C21 A:XBV1245 3.6 14.3 1.0 C20 A:XBV1245 3.6 17.3 1.0 C7 A:XBV1245 3.7 25.4 1.0 CB A:TRP215 3.8 14.4 1.0 O A:HOH2225 3.9 47.4 1.0 C23 A:XBV1245 4.1 16.0 1.0 CD2 A:TYR99 4.2 16.2 1.0 CE1 A:TYR99 4.3 20.2 1.0 O A:HOH2121 4.4 30.1 1.0 C2 A:XBV1245 4.5 20.3 1.0 O9 A:XBV1245 4.5 35.6 1.0 O A:SER214 4.6 16.2 1.0 CA A:TRP215 4.6 15.6 1.0 N25 A:XBV1245 4.8 16.7 1.0 CG A:TYR99 4.8 17.2 1.0 CD1 A:TYR99 4.9 19.1 1.0 CG A:TRP215 4.9 13.9 1.0

Fluorine binding site 2 out of 3 in the Factor Xa in Complex with A Pyrrolidine-3,4-Dicarboxylic Acid Inhibitor


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Factor Xa in Complex with A Pyrrolidine-3,4-Dicarboxylic Acid Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ A:F1245 b:31.9 occ:1.00 F35 A:XBV1245 0.0 31.9 1.0 C34 A:XBV1245 1.4 35.9 1.0 F36 A:XBV1245 2.2 46.0 1.0 C33 A:XBV1245 2.4 27.0 1.0 C5 A:XBV1245 2.8 22.9 1.0 N4 A:XBV1245 2.9 23.6 1.0 O A:GLU147 3.0 33.5 1.0 SG A:CYS191 3.4 23.1 1.0 SG A:CYS220 3.5 23.6 1.0 CD A:ARG143 3.5 29.6 1.0 CA A:GLU147 3.7 27.1 1.0 CG A:GLU147 3.7 30.7 1.0 C A:GLU147 3.8 34.3 1.0 CB A:GLN192 3.9 25.6 1.0 NE A:ARG143 4.0 34.0 1.0 N A:GLN192 4.3 23.1 1.0 CB A:GLU147 4.3 27.5 1.0 C1 A:XBV1245 4.3 18.8 1.0 NH1 A:ARG143 4.3 57.1 1.0 C3 A:XBV1245 4.3 21.1 1.0 CZ A:ARG143 4.4 57.8 1.0 CG A:ARG143 4.7 25.4 1.0 CA A:GLN192 4.8 23.2 1.0 OE1 A:GLN192 4.8 30.9 0.5 O A:HIS145 4.8 26.7 1.0 CB A:ARG143 4.9 21.1 1.0 N A:GLU147 4.9 27.1 1.0 CB A:CYS220 4.9 21.0 1.0 C6 A:XBV1245 4.9 22.3 1.0 CD A:GLN192 5.0 41.0 0.5

Fluorine binding site 3 out of 3 in the Factor Xa in Complex with A Pyrrolidine-3,4-Dicarboxylic Acid Inhibitor


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Factor Xa in Complex with A Pyrrolidine-3,4-Dicarboxylic Acid Inhibitor within 5.0Å range: probe atom residue distance (Å) B Occ A:F1245 b:46.0 occ:1.00 F36 A:XBV1245 0.0 46.0 1.0 C34 A:XBV1245 1.4 35.9 1.0 F35 A:XBV1245 2.2 31.9 1.0 C33 A:XBV1245 2.3 27.0 1.0 OE1 A:GLN192 2.8 30.9 0.5 N4 A:XBV1245 2.8 23.6 1.0 NE A:ARG143 2.9 34.0 1.0 CZ A:ARG143 3.0 57.8 1.0 CB A:GLN192 3.3 25.6 1.0 CD A:GLN192 3.3 41.0 0.5 CD A:ARG143 3.3 29.6 1.0 NH1 A:ARG143 3.4 57.1 1.0 NH2 A:ARG143 3.5 49.8 1.0 C5 A:XBV1245 3.7 22.9 1.0 CG A:GLN192 3.9 37.3 1.0 O A:GLU147 4.0 33.5 1.0 NE2 A:GLN192 4.0 37.7 0.5 C3 A:XBV1245 4.0 21.1 1.0 CG A:ARG143 4.6 25.4 1.0 CA A:GLN192 4.6 23.2 1.0 N A:GLN192 4.8 23.1 1.0 O A:HOH2226 4.9 56.8 1.0 C1 A:XBV1245 5.0 18.8 1.0

L.Anselm, D.W.Banner, J.Benz, K.Groebke Zbinden, J.Himber, H.Hilpert, W.Huber, B.Kuhn, J.L.Mary, M.B.Otteneder, N.Panday, F.Ricklin, M.Stahl, S.Thomi, W.Haap. Discovery of A Factor Xa Inhibitor (3R,4R)-1-(2,2-Difluoro-Ethyl)-Pyrrolidine-3,4-Dicarboxylic Acid 3-[(5-Chloro-Pyridin-2-Yl)-Amide] 4-{[2-Fluoro-4-(2-Oxo-2H-Pyridin-1-Yl)-Phenyl]-Amide} As A Clinical Candidate. Bioorg.Med.Chem. V. 20 5313 2010.
ISSN: ISSN 0968-0896
PubMed: 20650636
DOI: 10.1016/J.BMCL.2010.06.126