Chlorine in PDB 6us4: MTH1 in Complex with Compound 32

All present enzymatic activity of MTH1 in Complex with Compound 32:
3.6.1.55; 3.6.1.56;

The structure of MTH1 in Complex with Compound 32, PDB code: 6us4 was solved by Z.E.R.Newby, E.B.Lansdon, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	31.79 / 1.95
Space group	P 2 21 21
Cell size a, b, c (Å), α, β, γ (°)	36.235, 60.365, 66.286, 90.00, 90.00, 90.00
R / Rfree (%)	17.5 / 24.4

The binding sites of Chlorine atom in the MTH1 in Complex with Compound 32 (pdb code 6us4). This binding sites where shown within 5.0 Angstroms radius around Chlorine atom.
In total 2 binding sites of Chlorine where determined in the MTH1 in Complex with Compound 32, PDB code: 6us4:
Jump to Chlorine binding site number: 1; 2;

Chlorine binding site 1 out of 2 in the MTH1 in Complex with Compound 32


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 1 of MTH1 in Complex with Compound 32 within 5.0Å range: probe atom residue distance (Å) B Occ A:Cl201 b:14.8 occ:1.00 CL17 A:GN6201 0.0 14.8 1.0 C12 A:GN6201 1.7 18.9 1.0 C13 A:GN6201 2.7 19.1 1.0 C11 A:GN6201 2.7 12.5 1.0 C06 A:GN6201 3.1 15.3 1.0 N05 A:GN6201 3.1 10.5 1.0 CL18 A:GN6201 3.1 16.4 1.0 N01 A:GN6201 3.2 13.8 1.0 CG2 A:VAL83 3.7 10.8 1.0 CG1 A:VAL83 3.8 10.7 1.0 C07 A:GN6201 4.0 13.2 1.0 C14 A:GN6201 4.0 22.0 1.0 C16 A:GN6201 4.0 13.9 1.0 CE A:MET81 4.0 12.8 1.0 C04 A:GN6201 4.1 15.4 1.0 CE2 A:PHE72 4.2 10.2 1.0 C02 A:GN6201 4.2 13.4 1.0 CD2 A:LEU9 4.2 11.0 1.0 CB A:VAL83 4.3 9.2 1.0 C15 A:GN6201 4.5 19.8 1.0 CB A:LEU9 4.6 10.5 1.0 CD1 A:LEU9 4.6 16.0 1.0 CD2 A:PHE72 4.7 12.3 1.0 CG A:LEU9 4.7 11.9 1.0 N03 A:GN6201 4.7 11.0 1.0 ND2 A:ASN33 4.9 13.9 1.0 C08 A:GN6201 4.9 12.4 1.0 N10 A:GN6201 4.9 10.5 1.0 C09 A:GN6201 5.0 14.8 1.0

Chlorine binding site 2 out of 2 in the MTH1 in Complex with Compound 32


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 2 of MTH1 in Complex with Compound 32 within 5.0Å range: probe atom residue distance (Å) B Occ A:Cl201 b:16.4 occ:1.00 CL18 A:GN6201 0.0 16.4 1.0 C13 A:GN6201 1.7 19.1 1.0 C14 A:GN6201 2.7 22.0 1.0 C12 A:GN6201 2.7 18.9 1.0 CL17 A:GN6201 3.1 14.8 1.0 O A:THR8 3.2 12.2 1.0 N A:GLY37 3.6 17.6 1.0 C A:GLY36 3.8 23.7 1.0 C15 A:GN6201 4.0 19.8 1.0 C11 A:GN6201 4.0 12.5 1.0 CD2 A:TYR7 4.0 14.6 1.0 CA A:GLY37 4.1 19.4 1.0 CA A:GLY36 4.2 14.5 1.0 CD1 A:LEU9 4.3 16.0 1.0 O A:GLY36 4.3 14.2 1.0 C A:THR8 4.3 12.4 1.0 CB A:TYR7 4.3 14.1 1.0 CB A:LEU9 4.5 10.5 1.0 C16 A:GN6201 4.5 13.9 1.0 CG A:TYR7 4.6 14.8 1.0 CA A:LEU9 4.8 9.8 1.0 CE A:MET81 4.8 12.8 1.0 C A:GLY37 4.8 17.8 1.0 O A:HOH371 4.9 32.1 1.0 O A:GLY37 4.9 14.6 1.0 N A:GLY36 4.9 17.0 1.0 N A:THR8 4.9 11.4 1.0 CG A:LEU9 4.9 11.9 1.0 CE2 A:TYR7 5.0 15.1 1.0 N A:LEU9 5.0 11.1 1.0

J.Farand, J.E.Kropf, P.Blomgren, J.Xu, A.C.Schmitt, Z.E.Newby, T.Wang, E.Murakami, O.Barauskas, J.Sudhamsu, J.Y.Feng, A.Niedziela-Majka, B.E.Schultz, K.Schwartz, S.Viatchenko-Karpinski, D.Kornyeyev, A.Kashishian, P.Fan, X.Chen, E.B.Lansdon, M.O.Ports, K.S.Currie, W.J.Watkins, G.T.Notte. Discovery of Potent and Selective MTH1 Inhibitors For Oncology: Enabling Rapid Target (in)Validation. Acs Med.Chem.Lett. V. 11 358 2020.
ISSN: ISSN 1948-5875
PubMed: 32184970
DOI: 10.1021/ACSMEDCHEMLETT.9B00420