Vanadium in PDB 9f6c: Cardiac Myosin Motor Domain in the Pre-Powerstroke State Co- Crystallized with the Inhibitor Aficamten

The structure of Cardiac Myosin Motor Domain in the Pre-Powerstroke State Co- Crystallized with the Inhibitor Aficamten, PDB code: 9f6c was solved by J.Robert-Paganin, J.J.Hartman, B.P.Morgan, F.I.Malik, A.Houdusse, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	46.60 / 2.33
Space group	P 1 21 1
Cell size a, b, c (Å), α, β, γ (°)	69.424, 128.326, 103.53, 90, 91.47, 90
R / Rfree (%)	20.5 / 24.4

The structure of Cardiac Myosin Motor Domain in the Pre-Powerstroke State Co- Crystallized with the Inhibitor Aficamten also contains other interesting chemical elements:

Magnesium

(Mg)

2 atoms

The binding sites of Vanadium atom in the Cardiac Myosin Motor Domain in the Pre-Powerstroke State Co- Crystallized with the Inhibitor Aficamten (pdb code 9f6c). This binding sites where shown within 5.0 Angstroms radius around Vanadium atom.
In total 2 binding sites of Vanadium where determined in the Cardiac Myosin Motor Domain in the Pre-Powerstroke State Co- Crystallized with the Inhibitor Aficamten, PDB code: 9f6c:
Jump to Vanadium binding site number: 1; 2;

Vanadium binding site 1 out of 2 in the Cardiac Myosin Motor Domain in the Pre-Powerstroke State Co- Crystallized with the Inhibitor Aficamten


Mono view


Stereo pair view

A full contact list of Vanadium with other atoms in the V binding site number 1 of Cardiac Myosin Motor Domain in the Pre-Powerstroke State Co- Crystallized with the Inhibitor Aficamten within 5.0Å range: probe atom residue distance (Å) B Occ A:V1005 b:53.9 occ:1.00 V A:VO41005 0.0 53.9 1.0 O2 A:VO41005 1.6 50.3 1.0 O4 A:VO41005 1.6 43.9 1.0 O1 A:VO41005 1.6 48.4 1.0 O3 A:VO41005 1.6 61.2 1.0 O3B A:ADP1004 2.4 40.9 1.0 PB A:ADP1004 3.5 49.0 1.0 MG A:MG1002 3.5 53.1 1.0 O2B A:ADP1004 3.6 47.5 1.0 N A:SER242 3.7 47.2 1.0 OG A:SER241 3.7 58.7 1.0 OG A:SER180 3.8 59.6 1.0 ND2 A:ASN238 3.8 35.5 1.0 CA A:SER180 4.0 51.8 1.0 O A:HOH1101 4.0 44.3 1.0 N A:GLY464 4.1 50.1 1.0 CA A:SER241 4.1 44.3 1.0 N A:GLY181 4.2 50.6 1.0 CB A:SER180 4.3 52.6 1.0 NZ A:LYS184 4.3 39.5 1.0 CB A:SER241 4.3 46.9 1.0 C A:SER241 4.4 51.0 1.0 O1B A:ADP1004 4.4 48.3 1.0 OG A:SER242 4.4 56.6 1.0 CB A:SER242 4.4 47.2 1.0 O A:SER242 4.4 50.7 1.0 CA A:SER242 4.6 46.6 1.0 O A:HOH1105 4.6 46.5 1.0 O3A A:ADP1004 4.6 49.6 1.0 C A:SER180 4.6 55.5 1.0 CE A:LYS184 4.7 39.9 1.0 CA A:GLY464 4.8 50.3 1.0 CA A:ALA463 4.8 49.0 1.0 CG A:ASN238 4.8 49.2 1.0 CB A:ASN238 4.9 47.5 1.0 C A:ALA463 5.0 53.4 1.0 C A:SER242 5.0 52.5 1.0

Vanadium binding site 2 out of 2 in the Cardiac Myosin Motor Domain in the Pre-Powerstroke State Co- Crystallized with the Inhibitor Aficamten


Mono view


Stereo pair view

A full contact list of Vanadium with other atoms in the V binding site number 2 of Cardiac Myosin Motor Domain in the Pre-Powerstroke State Co- Crystallized with the Inhibitor Aficamten within 5.0Å range: probe atom residue distance (Å) B Occ B:V804 b:58.3 occ:1.00 V B:VO4804 0.0 58.3 1.0 O1 B:VO4804 1.6 52.5 1.0 O2 B:VO4804 1.6 54.7 1.0 O4 B:VO4804 1.6 50.0 1.0 O3 B:VO4804 1.6 65.1 1.0 O3B B:ADP803 2.5 50.2 1.0 MG B:MG801 3.4 53.7 1.0 PB B:ADP803 3.4 50.0 1.0 O2B B:ADP803 3.5 48.2 1.0 N B:SER242 3.8 49.8 1.0 OG B:SER241 3.8 63.5 1.0 OG B:SER180 3.8 68.5 1.0 N B:GLY464 3.9 57.2 1.0 ND2 B:ASN238 4.0 60.1 1.0 CA B:SER180 4.0 50.9 1.0 O B:HOH901 4.1 46.5 1.0 CB B:SER180 4.2 55.7 1.0 O1B B:ADP803 4.2 47.7 1.0 NZ B:LYS184 4.2 41.6 1.0 CA B:SER241 4.2 53.3 1.0 N B:GLY181 4.3 50.0 1.0 O B:HOH912 4.4 50.9 1.0 O B:SER242 4.4 53.1 1.0 CB B:SER242 4.4 51.1 1.0 OG B:SER242 4.5 62.1 1.0 CB B:SER241 4.5 56.6 1.0 C B:SER241 4.5 54.2 1.0 CE B:LYS184 4.6 39.8 1.0 CA B:SER242 4.6 48.3 1.0 CA B:GLY464 4.6 56.4 1.0 C B:SER180 4.7 54.0 1.0 O3A B:ADP803 4.7 56.4 1.0 CA B:ALA463 4.7 51.2 1.0 C B:ALA463 4.8 59.5 1.0 CG B:ASN238 5.0 66.7 1.0 C B:SER242 5.0 53.2 1.0

J.J.Hartman, D.T.Hwee, J.Robert-Paganin, C.Chuang, E.R.Chin, S.Edell, K.H.Lee, R.Madhvani, P.Paliwal, J.Pernier, S.S.Sarkar, J.Schaletzky, K.Schauer, K.D.Taheri, J.Wang, E.Wehri, Y.Wu, A.Houdusse, B.P.Morgan, F.I.Malik. Aficamten Is A Small-Molecule Cardiac Myosin Inhibitor Designed to Treat Hypertrophic Cardiomyopathy Nat Cardiovasc Res V. 3 1003 2024.
ISSN: ESSN 2731-0590
DOI: 10.1038/S44161-024-00505-0