Zinc in PDB 6h4s: Crystal Structure of Human KDM4A in Complex with Compound 16M

The structure of Crystal Structure of Human KDM4A in Complex with Compound 16M, PDB code: 6h4s was solved by Y.V.Le Bihan, R.L.M.Van Montfort, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	49.03 / 2.45
Space group	P 1 21 1
Cell size a, b, c (Å), α, β, γ (°)	57.690, 101.373, 142.930, 90.00, 99.25, 90.00
R / Rfree (%)	17.3 / 21.8

The structure of Crystal Structure of Human KDM4A in Complex with Compound 16M also contains other interesting chemical elements:

Chlorine

(Cl)

1 atom

The binding sites of Zinc atom in the Crystal Structure of Human KDM4A in Complex with Compound 16M (pdb code 6h4s). This binding sites where shown within 5.0 Angstroms radius around Zinc atom.
In total 8 binding sites of Zinc where determined in the Crystal Structure of Human KDM4A in Complex with Compound 16M, PDB code: 6h4s:
Jump to Zinc binding site number: 1; 2; 3; 4; 5; 6; 7; 8;

Zinc binding site 1 out of 8 in the Crystal Structure of Human KDM4A in Complex with Compound 16M


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 1 of Crystal Structure of Human KDM4A in Complex with Compound 16M within 5.0Å range: probe atom residue distance (Å) B Occ A:Zn401 b:38.1 occ:1.00 OE2 A:GLU190 2.1 44.0 1.0 N3 A:FQE403 2.1 46.2 0.9 N4 A:FQE403 2.1 42.1 0.9 NE2 A:HIS276 2.2 31.0 1.0 NE2 A:HIS188 2.2 31.5 1.0 N2 A:FQE403 2.9 44.3 0.9 C18 A:FQE403 2.9 42.5 0.9 CE1 A:HIS276 3.0 32.3 1.0 C19 A:FQE403 3.1 38.9 0.9 CE1 A:HIS188 3.1 30.4 1.0 CD A:GLU190 3.1 44.6 1.0 CD2 A:HIS276 3.2 30.0 1.0 C17 A:FQE403 3.2 47.8 0.9 CD2 A:HIS188 3.3 33.0 1.0 OE1 A:GLU190 3.6 39.4 1.0 C16 A:FQE403 4.1 45.7 0.9 O A:HOH523 4.2 45.4 1.0 ND1 A:HIS276 4.2 33.2 1.0 ND1 A:HIS188 4.3 31.2 1.0 C22 A:FQE403 4.3 39.0 0.9 CG A:HIS276 4.3 29.5 1.0 C15 A:FQE403 4.3 47.6 0.9 CG A:HIS188 4.3 31.5 1.0 C20 A:FQE403 4.4 36.2 0.9 CG A:GLU190 4.4 41.1 1.0 OG A:SER196 4.5 36.6 1.0 C21 A:FQE403 4.8 36.4 0.9

Zinc binding site 2 out of 8 in the Crystal Structure of Human KDM4A in Complex with Compound 16M


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 2 of Crystal Structure of Human KDM4A in Complex with Compound 16M within 5.0Å range: probe atom residue distance (Å) B Occ A:Zn402 b:58.1 occ:0.55 SG A:CYS234 2.1 80.3 1.0 SG A:CYS306 2.2 97.0 1.0 NE2 A:HIS240 2.5 62.0 1.0 SG A:CYS308 2.6 0.6 1.0 CB A:CYS234 3.1 78.1 1.0 CB A:CYS306 3.2 87.7 1.0 N A:CYS308 3.3 0.0 1.0 CD2 A:HIS240 3.4 59.8 1.0 N A:SER307 3.4 99.5 1.0 CE1 A:HIS240 3.5 61.8 1.0 CA A:CYS306 3.6 87.7 1.0 C A:CYS306 3.7 97.8 1.0 OG A:SER307 3.9 0.7 1.0 CB A:CYS308 3.9 0.8 1.0 CA A:CYS308 3.9 0.2 1.0 C A:CYS308 4.2 0.6 1.0 C A:SER307 4.2 0.2 1.0 CA A:SER307 4.3 0.7 1.0 CA A:CYS234 4.4 81.4 1.0 CG A:HIS240 4.5 56.6 1.0 O A:CYS306 4.6 97.3 1.0 O A:ALA236 4.6 66.2 1.0 ND1 A:HIS240 4.6 59.9 1.0 CB A:SER307 4.7 0.9 1.0

Zinc binding site 3 out of 8 in the Crystal Structure of Human KDM4A in Complex with Compound 16M


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 3 of Crystal Structure of Human KDM4A in Complex with Compound 16M within 5.0Å range: probe atom residue distance (Å) B Occ B:Zn401 b:28.8 occ:1.00 N3 B:FQE403 2.0 28.9 0.8 OE2 B:GLU190 2.1 26.9 1.0 N4 B:FQE403 2.1 22.7 0.8 NE2 B:HIS276 2.2 21.2 1.0 NE2 B:HIS188 2.2 26.2 1.0 N2 B:FQE403 2.8 23.3 0.8 C18 B:FQE403 2.9 21.7 0.8 CE1 B:HIS276 3.1 21.6 1.0 C19 B:FQE403 3.1 23.1 0.8 CE1 B:HIS188 3.1 25.3 1.0 CD B:GLU190 3.1 30.6 1.0 C17 B:FQE403 3.2 29.6 0.8 CD2 B:HIS188 3.3 27.5 1.0 CD2 B:HIS276 3.3 22.3 1.0 OE1 B:GLU190 3.5 28.6 1.0 C16 B:FQE403 4.1 24.8 0.8 C22 B:FQE403 4.2 23.0 0.8 ND1 B:HIS188 4.3 26.4 1.0 C15 B:FQE403 4.3 28.2 0.8 ND1 B:HIS276 4.3 23.8 1.0 O B:HOH552 4.3 17.1 1.0 CG B:HIS188 4.3 26.1 1.0 CG B:HIS276 4.4 22.0 1.0 C20 B:FQE403 4.4 21.6 0.8 CG B:GLU190 4.4 21.9 1.0 OG B:SER196 4.5 28.0 1.0 O B:HOH518 4.7 32.9 1.0 C21 B:FQE403 4.8 23.4 0.8

Zinc binding site 4 out of 8 in the Crystal Structure of Human KDM4A in Complex with Compound 16M


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 4 of Crystal Structure of Human KDM4A in Complex with Compound 16M within 5.0Å range: probe atom residue distance (Å) B Occ B:Zn402 b:34.5 occ:0.32 SG B:CYS306 2.2 78.6 1.0 NE2 B:HIS240 2.2 49.0 1.0 SG B:CYS234 2.2 58.9 1.0 SG B:CYS308 2.6 1.0 1.0 CD2 B:HIS240 3.1 47.8 1.0 CB B:CYS234 3.2 56.5 1.0 CE1 B:HIS240 3.2 48.7 1.0 CB B:CYS306 3.3 67.2 1.0 N B:CYS308 3.6 91.8 1.0 CA B:CYS306 3.7 66.0 1.0 N B:SER307 3.7 78.9 1.0 C B:CYS306 3.9 75.3 1.0 CB B:CYS308 4.0 0.3 1.0 OG B:SER307 4.1 0.2 1.0 CA B:CYS308 4.2 0.8 1.0 CG B:HIS240 4.3 45.6 1.0 C B:CYS308 4.3 0.1 1.0 ND1 B:HIS240 4.3 48.3 1.0 O B:ALA236 4.4 50.6 1.0 CA B:CYS234 4.5 58.5 1.0 C B:SER307 4.5 93.0 1.0 CA B:SER307 4.6 83.9 1.0 O B:CYS306 4.8 73.0 1.0 C B:ALA236 4.9 51.2 1.0

Zinc binding site 5 out of 8 in the Crystal Structure of Human KDM4A in Complex with Compound 16M


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 5 of Crystal Structure of Human KDM4A in Complex with Compound 16M within 5.0Å range: probe atom residue distance (Å) B Occ C:Zn401 b:37.1 occ:1.00 NE2 C:HIS276 2.1 29.4 1.0 N4 C:FQE403 2.1 46.7 0.9 OE2 C:GLU190 2.1 24.6 1.0 NE2 C:HIS188 2.2 35.8 1.0 N3 C:FQE403 2.3 54.6 0.9 CE1 C:HIS276 2.9 30.0 1.0 C18 C:FQE403 3.0 50.0 0.9 N2 C:FQE403 3.0 52.2 0.9 C19 C:FQE403 3.1 45.8 0.9 CE1 C:HIS188 3.1 34.5 1.0 CD2 C:HIS276 3.1 28.5 1.0 CD C:GLU190 3.2 42.7 1.0 CD2 C:HIS188 3.3 37.2 1.0 C17 C:FQE403 3.4 55.2 0.9 O C:HOH549 3.5 49.6 1.0 OE1 C:GLU190 3.6 46.6 1.0 ND1 C:HIS276 4.1 30.6 1.0 CG C:HIS276 4.2 27.6 1.0 ND1 C:HIS188 4.2 35.0 1.0 C16 C:FQE403 4.2 52.8 0.9 CG C:HIS188 4.3 34.2 1.0 C22 C:FQE403 4.3 49.9 0.9 C20 C:FQE403 4.4 47.1 0.9 O C:HOH527 4.4 40.4 1.0 CG C:GLU190 4.5 35.8 1.0 OG C:SER196 4.5 44.1 1.0 C15 C:FQE403 4.5 56.2 0.9 C21 C:FQE403 4.8 50.3 0.9 OG1 C:THR270 5.0 25.2 1.0

Zinc binding site 6 out of 8 in the Crystal Structure of Human KDM4A in Complex with Compound 16M


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 6 of Crystal Structure of Human KDM4A in Complex with Compound 16M within 5.0Å range: probe atom residue distance (Å) B Occ C:Zn402 b:44.9 occ:0.41 NE2 C:HIS240 2.1 75.0 1.0 SG C:CYS234 2.2 84.6 1.0 SG C:CYS306 2.3 88.1 1.0 SG C:CYS308 2.8 0.2 1.0 CB C:CYS234 3.0 82.2 1.0 CD2 C:HIS240 3.1 73.0 1.0 CE1 C:HIS240 3.1 74.0 1.0 CB C:CYS306 3.5 83.6 1.0 N C:CYS308 3.6 96.4 1.0 N C:SER307 3.8 93.7 1.0 CA C:CYS306 3.9 86.0 1.0 C C:CYS306 4.1 94.7 1.0 CB C:CYS308 4.2 1.0 1.0 CA C:CYS308 4.2 0.4 1.0 CG C:HIS240 4.3 69.5 1.0 ND1 C:HIS240 4.3 72.3 1.0 CA C:CYS234 4.3 85.7 1.0 O C:ALA236 4.6 70.2 1.0 C C:SER307 4.6 0.1 1.0 CA C:SER307 4.6 97.7 1.0 CB C:SER307 4.9 0.1 1.0 CA C:PHE237 5.0 64.7 1.0

Zinc binding site 7 out of 8 in the Crystal Structure of Human KDM4A in Complex with Compound 16M


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 7 of Crystal Structure of Human KDM4A in Complex with Compound 16M within 5.0Å range: probe atom residue distance (Å) B Occ D:Zn401 b:38.7 occ:1.00 N4 D:FQE403 2.1 36.5 0.8 N3 D:FQE403 2.1 42.0 0.8 NE2 D:HIS188 2.1 27.7 1.0 NE2 D:HIS276 2.1 26.3 1.0 OE2 D:GLU190 2.1 32.4 1.0 N2 D:FQE403 2.8 39.7 0.8 C18 D:FQE403 2.9 39.1 0.8 CE1 D:HIS188 3.0 25.6 1.0 CE1 D:HIS276 3.0 25.9 1.0 C19 D:FQE403 3.1 34.1 0.8 CD2 D:HIS276 3.2 25.1 1.0 CD2 D:HIS188 3.2 29.8 1.0 CD D:GLU190 3.2 43.5 1.0 C17 D:FQE403 3.3 42.8 0.8 OE1 D:GLU190 3.7 44.9 1.0 C16 D:FQE403 4.1 44.4 0.8 ND1 D:HIS188 4.1 26.2 1.0 ND1 D:HIS276 4.2 26.5 1.0 CG D:HIS188 4.2 27.4 1.0 C22 D:FQE403 4.2 38.0 0.8 CG D:HIS276 4.2 23.7 1.0 C15 D:FQE403 4.3 46.0 0.8 C20 D:FQE403 4.4 35.6 0.8 O D:HOH505 4.5 52.5 1.0 CG D:GLU190 4.5 41.8 1.0 OG D:SER196 4.6 35.2 1.0 O D:HOH555 4.7 30.1 1.0 C21 D:FQE403 4.8 37.1 0.8

Zinc binding site 8 out of 8 in the Crystal Structure of Human KDM4A in Complex with Compound 16M


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 8 of Crystal Structure of Human KDM4A in Complex with Compound 16M within 5.0Å range: probe atom residue distance (Å) B Occ D:Zn402 b:23.2 occ:0.27 NE2 D:HIS240 1.9 67.7 1.0 SG D:CYS234 2.1 76.2 1.0 SG D:CYS306 2.4 100.0 1.0 SG D:CYS308 2.6 0.7 1.0 CD2 D:HIS240 2.9 65.2 1.0 CE1 D:HIS240 3.0 67.0 1.0 CB D:CYS234 3.0 74.8 1.0 CB D:CYS306 3.5 93.2 1.0 N D:CYS308 3.8 96.0 1.0 N D:SER307 4.0 94.6 1.0 CA D:CYS306 4.0 92.3 1.0 CG D:HIS240 4.0 62.0 1.0 ND1 D:HIS240 4.1 65.0 1.0 CB D:CYS308 4.1 0.0 1.0 C D:CYS306 4.2 97.6 1.0 CA D:CYS308 4.3 0.8 1.0 CA D:CYS234 4.4 79.0 1.0 O D:ALA236 4.5 63.8 1.0 C D:CYS308 4.6 0.4 1.0 C D:SER307 4.7 99.7 1.0 CA D:SER307 4.8 95.2 1.0 CA D:PHE237 4.8 58.4 1.0 C D:ALA236 4.9 66.9 1.0

Y.V.Le Bihan, R.M.Lanigan, B.Atrash, M.G.Mclaughlin, S.Velupillai, A.G.Malcolm, K.S.England, G.F.Ruda, N.Y.Mok, A.Tumber, K.Tomlin, H.Saville, E.Shehu, C.Mcandrew, L.Carmichael, J.M.Bennett, F.Jeganathan, P.Eve, A.Donovan, A.Hayes, F.Wood, F.I.Raynaud, O.Fedorov, P.E.Brennan, R.Burke, R.L.M.Van Montfort, O.W.Rossanese, J.Blagg, V.Bavetsias. C8-Substituted Pyrido[3,4-D]Pyrimidin-4(3H)-Ones: Studies Towards the Identification of Potent, Cell Penetrant Jumonji C Domain Containing Histone Lysine Demethylase 4 Subfamily (KDM4) Inhibitors, Compound Profiling in Cell-Based Target Engagement Assays. Eur.J.Med.Chem. V. 177 316 2019.
ISSN: ISSN 0223-5234
PubMed: 31158747
DOI: 10.1016/J.EJMECH.2019.05.041