Zinc in PDB 5arf: SMYD2 in Complex with Small Molecule Inhibitor Compound-2

All present enzymatic activity of SMYD2 in Complex with Small Molecule Inhibitor Compound-2:
2.1.1.43;

The structure of SMYD2 in Complex with Small Molecule Inhibitor Compound-2, PDB code: 5arf was solved by R.C.Hillig, V.Badock, N.Barak, T.Stellfeld, E.Eggert, A.Ter Laak, J.Weiske, C.D.Christ, S.Koehr, D.Stoeckigt, J.Mowat, T.Mueller, A.E.Fernandez-Montalvan, I.V.Hartung, C.Stresemann, T.Brumby, H.Weinmann, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	47.59 / 1.92
Space group	P 21 21 21
Cell size a, b, c (Å), α, β, γ (°)	130.493, 51.759, 69.568, 90.00, 90.00, 90.00
R / Rfree (%)	25.7 / 30.1

The structure of SMYD2 in Complex with Small Molecule Inhibitor Compound-2 also contains other interesting chemical elements:

Fluorine	(F)	2 atoms
Chlorine	(Cl)	1 atom

The binding sites of Zinc atom in the SMYD2 in Complex with Small Molecule Inhibitor Compound-2 (pdb code 5arf). This binding sites where shown within 5.0 Angstroms radius around Zinc atom.
In total 3 binding sites of Zinc where determined in the SMYD2 in Complex with Small Molecule Inhibitor Compound-2, PDB code: 5arf:
Jump to Zinc binding site number: 1; 2; 3;

Zinc binding site 1 out of 3 in the SMYD2 in Complex with Small Molecule Inhibitor Compound-2


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 1 of SMYD2 in Complex with Small Molecule Inhibitor Compound-2 within 5.0Å range: probe atom residue distance (Å) B Occ A:Zn1003 b:35.8 occ:0.80 SG A:CYS267 2.1 62.1 1.0 SG A:CYS264 2.2 64.8 1.0 SG A:CYS262 2.3 62.9 1.0 SG A:CYS209 2.4 53.7 1.0 CB A:CYS267 2.5 69.6 1.0 CB A:CYS264 3.0 66.3 1.0 CB A:CYS209 3.0 52.6 1.0 CB A:CYS262 3.2 64.4 1.0 N A:CYS209 3.4 51.0 1.0 N A:CYS264 3.5 74.5 1.0 CA A:CYS264 3.8 73.1 1.0 CA A:CYS209 3.8 49.2 1.0 CA A:CYS267 4.0 73.7 1.0 N A:CYS267 4.1 72.3 1.0 C A:CYS262 4.4 75.2 1.0 CA A:CYS262 4.4 69.9 1.0 C A:CYS264 4.4 76.4 1.0 N A:GLU263 4.5 77.1 1.0 NE2 A:HIS207 4.5 47.1 1.0 C A:SER208 4.5 48.5 1.0 O A:CYS264 4.5 79.2 1.0 C A:GLU263 4.6 81.2 1.0 CA A:SER208 4.7 51.5 1.0 CD2 A:HIS207 4.7 49.3 1.0 OG A:SER208 4.7 56.3 1.0 O A:CYS262 4.7 78.0 1.0 NH2 A:ARG250 4.8 60.8 1.0 C A:CYS209 4.9 48.9 1.0 CA A:GLU263 4.9 83.2 1.0 CB A:GLU266 5.0 62.8 1.0

Zinc binding site 2 out of 3 in the SMYD2 in Complex with Small Molecule Inhibitor Compound-2


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 2 of SMYD2 in Complex with Small Molecule Inhibitor Compound-2 within 5.0Å range: probe atom residue distance (Å) B Occ A:Zn1004 b:19.5 occ:0.80 SG A:CYS55 2.1 33.1 1.0 SG A:CYS78 2.1 40.6 1.0 SG A:CYS74 2.4 40.8 1.0 SG A:CYS52 2.4 35.9 1.0 CB A:CYS55 3.2 31.1 1.0 CB A:CYS74 3.2 45.5 1.0 CB A:CYS52 3.2 33.9 1.0 CB A:CYS78 3.4 42.0 1.0 N A:CYS55 3.9 29.0 1.0 N A:CYS74 4.1 44.5 1.0 CA A:CYS55 4.1 28.2 1.0 CA A:CYS74 4.3 47.1 1.0 OG1 A:THR57 4.7 32.3 1.0 CA A:CYS78 4.7 43.1 1.0 CB A:TYR54 4.7 33.8 1.0 CA A:CYS52 4.7 33.1 1.0 CB A:THR57 4.8 32.9 1.0 C A:CYS55 4.8 26.5 1.0 C A:TYR54 4.9 28.2 1.0 CD2 A:TYR54 5.0 37.8 1.0

Zinc binding site 3 out of 3 in the SMYD2 in Complex with Small Molecule Inhibitor Compound-2


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 3 of SMYD2 in Complex with Small Molecule Inhibitor Compound-2 within 5.0Å range: probe atom residue distance (Å) B Occ A:Zn1005 b:17.0 occ:0.60 SG A:CYS68 1.8 51.5 1.0 SG A:CYS65 2.0 54.6 1.0 NE2 A:HIS86 2.1 44.0 1.0 SG A:CYS90 2.5 52.5 1.0 CD2 A:HIS86 2.9 42.3 1.0 CB A:CYS65 3.0 53.8 1.0 CE1 A:HIS86 3.3 41.5 1.0 CB A:CYS90 3.4 47.5 1.0 CB A:CYS68 3.5 55.0 1.0 N A:CYS68 3.8 63.5 1.0 CG A:ARG67 4.0 67.4 1.0 CG A:HIS86 4.1 38.7 1.0 CA A:CYS90 4.2 47.1 1.0 ND1 A:HIS86 4.3 38.3 1.0 CA A:CYS68 4.3 61.2 1.0 CA A:CYS65 4.4 58.0 1.0 CD A:ARG67 4.6 69.2 1.0 NE A:ARG67 4.6 71.0 1.0 CZ3 A:TRP83 4.6 47.2 1.0 C A:CYS65 4.8 63.0 1.0 CB A:ALA71 4.9 42.1 1.0 C A:ARG67 5.0 69.7 1.0 C A:CYS90 5.0 51.1 1.0

E.Eggert, R.C.Hillig, S.Kohr, D.Stockigt, J.Weiske, N.Barak, J.Mowat, T.Brumby, C.D.Christ, A.Ter Laak, T.Lang, A.E.Fernandez-Montalvan, V.Badock, H.Weinmann, I.V.Hartung, D.Barsyte-Lovejoy, M.Szewczyk, S.Kennedy, F.Li, M.Vedadi, P.J.Brown, V.Santhakumar, C.H.Arrowsmith, T.Stellfeld, C.Stresemann. Discovery and Characterization of A Highly Potent and Selective Aminopyrazoline-Based in Vivo Probe (Bay-598) For the Protein Lysine Methyltransferase SMYD2. J.Med.Chem. V. 59 4578 2016.
ISSN: ISSN 0022-2623
PubMed: 27075367
DOI: 10.1021/ACS.JMEDCHEM.5B01890