Fluorine in PDB 8uvl: Crystal Structure of Selective IRE1A Inhibitor 29 at the Enzyme Active Site

All present enzymatic activity of Crystal Structure of Selective IRE1A Inhibitor 29 at the Enzyme Active Site:
2.7.11.1;

The structure of Crystal Structure of Selective IRE1A Inhibitor 29 at the Enzyme Active Site, PDB code: 8uvl was solved by J.R.Kiefer, H.A.Wallweber, M.-G.Braun, W.Wei, F.Jiang, W.Wang, J.Rudolph, A.Ashkenazi, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	32.41 / 2.43
Space group	C 2 2 21
Cell size a, b, c (Å), α, β, γ (°)	67.89, 166.834, 102.95, 90, 90, 90
R / Rfree (%)	18.1 / 25.1

The binding sites of Fluorine atom in the Crystal Structure of Selective IRE1A Inhibitor 29 at the Enzyme Active Site (pdb code 8uvl). 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 Selective IRE1A Inhibitor 29 at the Enzyme Active Site, PDB code: 8uvl:
Jump to Fluorine binding site number: 1; 2; 3; 4;

Fluorine binding site 1 out of 4 in the Crystal Structure of Selective IRE1A Inhibitor 29 at the Enzyme Active Site


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 Selective IRE1A Inhibitor 29 at the Enzyme Active Site within 5.0Å range: probe atom residue distance (Å) B Occ A:F1009 b:77.8 occ:1.00 F1 A:XOE1009 0.0 77.8 1.0 C4 A:XOE1009 1.4 69.3 1.0 C8 A:XOE1009 2.3 57.7 1.0 C3 A:XOE1009 2.4 68.0 1.0 N9 A:XOE1009 2.4 84.2 1.0 F2 A:XOE1009 2.7 79.3 1.0 CB A:LYS599 3.3 72.5 1.0 C5 A:XOE1009 3.6 66.6 1.0 C7 A:XOE1009 3.6 73.5 1.0 CG2 A:ILE642 3.7 64.5 1.0 CG2 A:ILE640 3.7 70.5 1.0 CD1 A:ILE642 3.8 62.3 1.0 O A:ILE640 3.8 75.4 1.0 CG1 A:ILE642 3.8 63.2 1.0 CD A:LYS599 3.9 79.8 1.0 S30 A:XOE1009 4.0 69.2 1.0 C6 A:XOE1009 4.1 70.8 1.0 CB A:ILE640 4.2 72.8 1.0 N A:LYS599 4.2 72.6 1.0 CG A:LYS599 4.2 73.4 1.0 CB A:ILE642 4.4 63.2 1.0 CA A:LYS599 4.4 73.8 1.0 C A:ILE640 4.6 71.8 1.0 C31 A:XOE1009 4.6 81.4 1.0 O10 A:XOE1009 4.7 65.2 1.0 O32 A:XOE1009 4.8 77.9 1.0 F40 A:XOE1009 4.8 72.4 1.0 O33 A:XOE1009 4.9 84.2 1.0 C35 A:XOE1009 4.9 75.4 1.0 O A:ALA597 4.9 67.4 1.0

Fluorine binding site 2 out of 4 in the Crystal Structure of Selective IRE1A Inhibitor 29 at the Enzyme Active Site


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 Selective IRE1A Inhibitor 29 at the Enzyme Active Site within 5.0Å range: probe atom residue distance (Å) B Occ A:F1009 b:79.3 occ:1.00 F2 A:XOE1009 0.0 79.3 1.0 C3 A:XOE1009 1.4 68.0 1.0 C4 A:XOE1009 2.3 69.3 1.0 C5 A:XOE1009 2.4 66.6 1.0 O10 A:XOE1009 2.6 65.2 1.0 F1 A:XOE1009 2.7 77.8 1.0 CG1 A:VAL586 3.4 68.5 1.0 C8 A:XOE1009 3.6 57.7 1.0 CD1 A:ILE642 3.6 62.3 1.0 C6 A:XOE1009 3.6 70.8 1.0 CB A:ALA597 3.7 64.7 1.0 CG1 A:ILE642 3.7 63.2 1.0 CB A:LYS599 3.8 72.5 1.0 CG2 A:VAL586 3.8 70.4 1.0 N A:LYS599 3.9 72.6 1.0 C11 A:XOE1009 3.9 56.1 1.0 C A:ALA597 4.0 72.5 1.0 O A:ALA597 4.0 67.4 1.0 N A:VAL598 4.1 69.6 1.0 C7 A:XOE1009 4.1 73.5 1.0 C18 A:XOE1009 4.2 49.0 1.0 CB A:VAL586 4.2 71.8 1.0 CA A:LYS599 4.2 73.8 1.0 C A:VAL598 4.3 72.6 1.0 CA A:ALA597 4.5 66.1 1.0 N16 A:XOE1009 4.6 61.1 1.0 N9 A:XOE1009 4.6 84.2 1.0 CA A:VAL598 4.6 71.6 1.0 CG A:LYS599 4.6 73.4 1.0 O A:ILE640 4.7 75.4 1.0 CD A:LYS599 4.8 79.8 1.0 C12 A:XOE1009 4.8 67.6 1.0 C17 A:XOE1009 4.8 59.7 1.0 O A:VAL598 4.9 75.1 1.0 C19 A:XOE1009 4.9 55.4 1.0 CB A:ILE642 5.0 63.2 1.0

Fluorine binding site 3 out of 4 in the Crystal Structure of Selective IRE1A Inhibitor 29 at the Enzyme Active Site


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 Selective IRE1A Inhibitor 29 at the Enzyme Active Site within 5.0Å range: probe atom residue distance (Å) B Occ A:F1009 b:72.4 occ:1.00 F40 A:XOE1009 0.0 72.4 1.0 C7 A:XOE1009 1.4 73.5 1.0 C6 A:XOE1009 2.4 70.8 1.0 C8 A:XOE1009 2.4 57.7 1.0 O33 A:XOE1009 2.9 84.2 1.0 O32 A:XOE1009 3.0 77.9 1.0 N A:ASP711 3.0 59.5 1.0 CA A:ASP711 3.1 53.4 1.0 N9 A:XOE1009 3.1 84.2 1.0 S30 A:XOE1009 3.2 69.2 1.0 CB A:ASP711 3.4 51.3 1.0 OG A:SER710 3.6 61.6 1.0 C5 A:XOE1009 3.6 66.6 1.0 C4 A:XOE1009 3.7 69.3 1.0 CB A:SER710 3.8 51.1 1.0 O A:HOH1103 3.8 91.4 1.0 CG A:ASP711 3.9 62.2 1.0 NZ A:LYS599 4.0 83.9 1.0 C A:SER710 4.0 51.1 1.0 OD1 A:ASP711 4.1 72.8 1.0 C3 A:XOE1009 4.1 68.0 1.0 C A:ASP711 4.5 51.7 1.0 CA A:SER710 4.5 82.0 1.0 OD2 A:ASP711 4.6 73.4 1.0 F1 A:XOE1009 4.8 77.8 1.0 O10 A:XOE1009 4.8 65.2 1.0 O A:SER710 4.9 62.3 1.0 N A:PHE712 4.9 62.5 1.0 CD A:LYS599 5.0 79.8 1.0 C31 A:XOE1009 5.0 81.4 1.0

Fluorine binding site 4 out of 4 in the Crystal Structure of Selective IRE1A Inhibitor 29 at the Enzyme Active Site


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 Selective IRE1A Inhibitor 29 at the Enzyme Active Site within 5.0Å range: probe atom residue distance (Å) B Occ A:F1009 b:64.9 occ:1.00 F41 A:XOE1009 0.0 64.9 1.0 C26 A:XOE1009 1.4 57.5 1.0 C25 A:XOE1009 2.3 49.0 1.0 C27 A:XOE1009 2.3 66.4 1.0 C24 A:XOE1009 2.6 63.1 1.0 N28 A:XOE1009 3.1 60.1 1.0 C29 A:XOE1009 3.4 50.9 1.0 CD2 A:LEU577 3.4 66.0 1.0 O A:HOH1176 3.7 78.1 1.0 N23 A:XOE1009 3.9 64.7 1.0 CB A:LEU577 4.3 78.5 1.0 CG A:LEU577 4.4 78.6 1.0 CA A:LEU577 4.4 68.7 1.0 O A:LEU577 4.5 73.8 1.0 OE1 A:GLU651 4.8 69.9 1.0 C21 A:XOE1009 4.9 62.3 1.0 N22 A:XOE1009 4.9 65.7 1.0 CD1 A:LEU577 5.0 65.5 1.0

M.G.Braun, A.Ashkenazi, R.E.Beveridge, G.Castanedo, H.A.Wallweber, M.H.Beresini, K.R.Clark, T.De Bruyn, L.Fu, P.Gibbons, F.Jiang, S.Kaufman, D.Kan, J.R.Kiefer, J.P.Leclerc, A.Lemire, C.Ly, E.Segal, J.Sims, W.Wang, W.Wei, L.Zhao, J.B.Schwarz, J.Rudolph. Discovery of Potent, Selective, and Orally Available IRE1 Alpha Inhibitors Demonstrating Comparable Pd Modulation to IRE1 Knockdown in A Multiple Myeloma Model. J.Med.Chem. 2024.
ISSN: ISSN 0022-2623
PubMed: 38748820
DOI: 10.1021/ACS.JMEDCHEM.3C02425