Magnesium 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:

Vanadium

(V)

2 atoms

The binding sites of Magnesium 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 Magnesium atom.
In total 2 binding sites of Magnesium where determined in the Cardiac Myosin Motor Domain in the Pre-Powerstroke State Co- Crystallized with the Inhibitor Aficamten, PDB code: 9f6c:
Jump to Magnesium binding site number: 1; 2;

Magnesium 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 Magnesium with other atoms in the Mg 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:Mg1002 b:53.1 occ:1.00 OG A:SER242 1.9 56.6 1.0 OG1 A:THR185 1.9 58.5 1.0 O2B A:ADP1004 2.1 47.5 1.0 O2 A:VO41005 2.1 50.3 1.0 O A:HOH1101 2.2 44.3 1.0 O A:HOH1105 2.5 46.5 1.0 CB A:SER242 3.0 47.2 1.0 CB A:THR185 3.2 55.0 1.0 PB A:ADP1004 3.5 49.0 1.0 V A:VO41005 3.5 53.9 1.0 N A:SER242 3.7 47.2 1.0 O3B A:ADP1004 3.8 40.9 1.0 CA A:SER242 3.9 46.6 1.0 OD1 A:ASP461 4.0 58.6 1.0 N A:THR185 4.1 43.3 1.0 CG2 A:THR185 4.1 50.8 1.0 O1 A:VO41005 4.1 48.4 1.0 OD2 A:ASP461 4.2 60.4 1.0 CA A:THR185 4.2 44.1 1.0 O A:HOH1115 4.3 45.7 1.0 O3 A:VO41005 4.3 61.2 1.0 O2A A:ADP1004 4.3 50.9 1.0 O3A A:ADP1004 4.4 49.6 1.0 CG A:ASP461 4.5 58.0 1.0 O1B A:ADP1004 4.6 48.3 1.0 O4 A:VO41005 4.7 43.9 1.0 O A:ILE462 4.7 47.5 1.0 O A:HOH1134 4.7 42.0 1.0 O A:ASN240 4.7 47.2 1.0 PA A:ADP1004 4.8 49.9 1.0 C A:SER241 4.8 51.0 1.0 ND2 A:ASN238 5.0 35.5 1.0 O1A A:ADP1004 5.0 46.1 1.0

Magnesium 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 Magnesium with other atoms in the Mg 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:Mg801 b:53.7 occ:1.00 OG B:SER242 1.9 62.1 1.0 O2 B:VO4804 1.9 54.7 1.0 O2B B:ADP803 2.1 48.2 1.0 OG1 B:THR185 2.1 52.0 1.0 O B:HOH901 2.3 46.5 1.0 O B:HOH912 2.3 50.9 1.0 CB B:SER242 2.9 51.1 1.0 CB B:THR185 3.3 53.7 1.0 V B:VO4804 3.4 58.3 1.0 PB B:ADP803 3.4 50.0 1.0 N B:SER242 3.6 49.8 1.0 O3B B:ADP803 3.7 50.2 1.0 CA B:SER242 3.8 48.3 1.0 O1 B:VO4804 3.9 52.5 1.0 OD1 B:ASP461 4.1 61.8 1.0 O3 B:VO4804 4.2 65.1 1.0 CG2 B:THR185 4.2 52.4 1.0 O2A B:ADP803 4.2 48.6 1.0 N B:THR185 4.2 49.3 1.0 OD2 B:ASP461 4.3 68.9 1.0 CA B:THR185 4.3 48.7 1.0 O B:HOH902 4.3 49.3 1.0 O3A B:ADP803 4.4 56.4 1.0 O4 B:VO4804 4.4 50.0 1.0 O1B B:ADP803 4.5 47.7 1.0 O B:HOH909 4.6 49.8 1.0 CG B:ASP461 4.6 60.1 1.0 O B:ASN240 4.7 57.1 1.0 C B:SER241 4.7 54.2 1.0 O B:ILE462 4.7 52.8 1.0 PA B:ADP803 4.8 56.6 1.0 ND2 B:ASN238 4.8 60.1 1.0 O1A B:ADP803 4.9 60.2 1.0 C B:SER242 4.9 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