Fluorine in PDB 8b2t: Sars-Cov-2 Main Protease (Mpro) in Complex with Nirmatrelvir Alkyne

All present enzymatic activity of Sars-Cov-2 Main Protease (Mpro) in Complex with Nirmatrelvir Alkyne:
3.4.22.69;

The structure of Sars-Cov-2 Main Protease (Mpro) in Complex with Nirmatrelvir Alkyne, PDB code: 8b2t was solved by C.D.Owen, A.D.Crawshaw, A.J.Warren, J.Trincao, Y.Zhao, L.Brewitz, T.R.Malla, E.Salah, L.Petra, C.Strain-Damerell, C.J.Schofield, M.A.Walsh, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	22.48 / 1.89
Space group	P 21 21 2
Cell size a, b, c (Å), α, β, γ (°)	46.037, 64.392, 104.952, 90, 90, 90
R / Rfree (%)	18.2 / 22.3

The binding sites of Fluorine atom in the Sars-Cov-2 Main Protease (Mpro) in Complex with Nirmatrelvir Alkyne (pdb code 8b2t). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 3 binding sites of Fluorine where determined in the Sars-Cov-2 Main Protease (Mpro) in Complex with Nirmatrelvir Alkyne, PDB code: 8b2t:
Jump to Fluorine binding site number: 1; 2; 3;

Fluorine binding site 1 out of 3 in the Sars-Cov-2 Main Protease (Mpro) in Complex with Nirmatrelvir Alkyne


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Sars-Cov-2 Main Protease (Mpro) in Complex with Nirmatrelvir Alkyne within 5.0Å range: probe atom residue distance (Å) B Occ A:F401 b:46.4 occ:1.00 F1 A:OW1401 0.0 46.4 1.0 C17 A:OW1401 1.3 34.7 1.0 F2 A:OW1401 2.1 44.0 1.0 F3 A:OW1401 2.1 50.2 1.0 C16 A:OW1401 2.4 30.9 1.0 O A:GLU166 2.8 25.2 1.0 N4 A:OW1401 2.8 19.4 1.0 CD2 A:LEU167 3.2 23.4 1.0 CE A:MET165 3.4 41.1 1.0 O4 A:OW1401 3.4 34.8 1.0 C A:GLU166 3.5 22.6 1.0 CA A:LEU167 3.6 27.4 1.0 N A:LEU167 3.9 20.5 1.0 CG A:LEU167 3.9 27.3 1.0 C15 A:OW1401 4.2 21.9 1.0 CB A:LEU167 4.3 25.9 1.0 SD A:MET165 4.4 36.0 1.0 N A:GLU166 4.5 20.6 1.0 CG A:MET165 4.5 27.0 1.0 CB A:MET165 4.6 24.6 1.0 CA A:GLU166 4.6 18.5 1.0 CB A:GLN192 4.7 40.9 1.0 O3 A:OW1401 4.7 22.6 1.0 C14 A:OW1401 4.7 20.5 1.0 CD A:PRO168 4.7 39.3 1.0 NE2 A:GLN192 4.7 27.2 1.0 C A:LEU167 4.8 33.3 1.0

Fluorine binding site 2 out of 3 in the Sars-Cov-2 Main Protease (Mpro) in Complex with Nirmatrelvir Alkyne


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Sars-Cov-2 Main Protease (Mpro) in Complex with Nirmatrelvir Alkyne within 5.0Å range: probe atom residue distance (Å) B Occ A:F401 b:44.0 occ:1.00 F2 A:OW1401 0.0 44.0 1.0 C17 A:OW1401 1.3 34.7 1.0 F1 A:OW1401 2.1 46.4 1.0 F3 A:OW1401 2.2 50.2 1.0 C16 A:OW1401 2.3 30.9 1.0 O4 A:OW1401 2.6 34.8 1.0 O A:THR190 3.0 43.1 1.0 NE2 A:GLN192 3.4 27.2 1.0 N4 A:OW1401 3.5 19.4 1.0 CE A:MET165 3.6 41.1 1.0 CB A:GLN192 3.6 40.9 1.0 CG A:GLN192 3.8 35.3 1.0 CD A:GLN192 3.8 26.0 1.0 O A:ARG188 4.2 28.5 1.0 N A:GLN192 4.2 30.5 1.0 C A:THR190 4.2 50.8 1.0 CD2 A:LEU167 4.3 23.4 1.0 N A:THR190 4.3 37.3 1.0 CA A:GLN192 4.4 38.2 1.0 O A:GLU166 4.7 25.2 1.0 C15 A:OW1401 4.7 21.9 1.0 O A:GLN192 4.7 40.5 1.0 OE1 A:GLN192 4.8 28.6 1.0 C A:GLN192 5.0 36.7 1.0 C A:ALA191 5.0 41.6 1.0 CA A:THR190 5.0 51.3 1.0

Fluorine binding site 3 out of 3 in the Sars-Cov-2 Main Protease (Mpro) in Complex with Nirmatrelvir Alkyne


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Sars-Cov-2 Main Protease (Mpro) in Complex with Nirmatrelvir Alkyne within 5.0Å range: probe atom residue distance (Å) B Occ A:F401 b:50.2 occ:1.00 F3 A:OW1401 0.0 50.2 1.0 C17 A:OW1401 1.3 34.7 1.0 F1 A:OW1401 2.1 46.4 1.0 F2 A:OW1401 2.2 44.0 1.0 C16 A:OW1401 2.3 30.9 1.0 O4 A:OW1401 3.1 34.8 1.0 N4 A:OW1401 3.1 19.4 1.0 O A:GLU166 3.6 25.2 1.0 CD A:PRO168 3.9 39.3 1.0 O A:THR190 4.1 43.1 1.0 CA A:LEU167 4.2 27.4 1.0 O A:GLN192 4.2 40.5 1.0 C15 A:OW1401 4.4 21.9 1.0 CD2 A:LEU167 4.4 23.4 1.0 C19 A:OW1401 4.4 24.2 1.0 CG A:PRO168 4.5 36.7 1.0 C A:GLU166 4.5 22.6 1.0 N A:PRO168 4.6 30.7 1.0 N A:GLN192 4.6 30.5 1.0 CB A:GLN192 4.7 40.9 1.0 C A:LEU167 4.7 33.3 1.0 N A:LEU167 4.8 20.5 1.0 C18 A:OW1401 4.9 21.3 1.0 C A:GLN192 5.0 36.7 1.0

L.Brewitz, L.Dumjahn, Y.Zhao, C.D.Owen, S.M.Laidlaw, T.R.Malla, D.Nguyen, P.Lukacik, E.Salah, A.D.Crawshaw, A.J.Warren, J.Trincao, C.Strain-Damerell, M.W.Carroll, M.A.Walsh, C.J.Schofield. Alkyne Derivatives of Sars-Cov-2 Main Protease Inhibitors Including Nirmatrelvir Inhibit By Reacting Covalently with the Nucleophilic Cysteine. J.Med.Chem. 2023.
ISSN: ISSN 0022-2623
PubMed: 36757959
DOI: 10.1021/ACS.JMEDCHEM.2C01627