Zinc in PDB 4w2r: Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-2-[(4-Methoxy-6- Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl)Methyl]-7-[(R)-Methoxy(Oxetan-3- Yl)Methyl]-3,4-Dihydroisoquinolin-1(2H)-One

The structure of Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-2-[(4-Methoxy-6- Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl)Methyl]-7-[(R)-Methoxy(Oxetan-3- Yl)Methyl]-3,4-Dihydroisoquinolin-1(2H)-One, PDB code: 4w2r was solved by K.S.Gajiwala, A.Brooun, W.Liu, Y.Deng, A.E.Stewart, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	148.01 / 2.81
Space group	P 1 21 1
Cell size a, b, c (Å), α, β, γ (°)	70.720, 115.484, 151.538, 90.00, 102.40, 90.00
R / Rfree (%)	n/a / n/a

The structure of Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-2-[(4-Methoxy-6- Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl)Methyl]-7-[(R)-Methoxy(Oxetan-3- Yl)Methyl]-3,4-Dihydroisoquinolin-1(2H)-One also contains other interesting chemical elements:

Chlorine

(Cl)

4 atoms

Pages:

>>> Page 1 <<< Page 2, Binding sites: 11 - 14;

Binding sites:

The binding sites of Zinc atom in the Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-2-[(4-Methoxy-6- Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl)Methyl]-7-[(R)-Methoxy(Oxetan-3- Yl)Methyl]-3,4-Dihydroisoquinolin-1(2H)-One (pdb code 4w2r). This binding sites where shown within 5.0 Angstroms radius around Zinc atom.
In total 14 binding sites of Zinc where determined in the Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-2-[(4-Methoxy-6- Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl)Methyl]-7-[(R)-Methoxy(Oxetan-3- Yl)Methyl]-3,4-Dihydroisoquinolin-1(2H)-One, PDB code: 4w2r:
Jump to Zinc binding site number: 1; 2; 3; 4; 5; 6; 7; 8; 9; 10;

Zinc binding site 1 out of 14 in the Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-2-[(4-Methoxy-6- Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl)Methyl]-7-[(R)-Methoxy(Oxetan-3- Yl)Methyl]-3,4-Dihydroisoquinolin-1(2H)-One


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 1 of Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-2-[(4-Methoxy-6- Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl)Methyl]-7-[(R)-Methoxy(Oxetan-3- Yl)Methyl]-3,4-Dihydroisoquinolin-1(2H)-One within 5.0Å range: probe atom residue distance (Å) B Occ A:Zn701 b:75.7 occ:0.74 SG A:CYS427 2.5 77.2 1.0 SG A:CYS420 2.5 63.9 1.0 SG A:CYS431 2.5 79.9 1.0 NE2 A:HIS422 2.5 81.4 1.0 CE1 A:HIS422 2.9 82.1 1.0 CB A:CYS420 3.2 65.0 1.0 CD2 A:HIS422 3.5 81.5 1.0 CB A:CYS427 3.6 81.4 1.0 CB A:CYS431 3.7 78.9 1.0 ZN A:ZN702 3.8 65.9 0.8 ZN A:ZN703 3.9 77.3 0.8 ND1 A:HIS422 3.9 82.3 1.0 CA A:CYS427 4.2 82.5 1.0 SG A:CYS440 4.2 57.9 1.0 CG A:HIS422 4.2 81.0 1.0 CA A:CYS431 4.6 79.3 1.0 CA A:CYS420 4.6 65.4 1.0 CD A:PRO432 4.7 77.4 1.0 SG A:CYS433 4.7 67.1 1.0 CB A:CYS433 4.7 71.8 1.0 CB A:CYS446 4.9 71.8 1.0 N A:CYS427 4.9 84.5 1.0

Zinc binding site 2 out of 14 in the Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-2-[(4-Methoxy-6- Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl)Methyl]-7-[(R)-Methoxy(Oxetan-3- Yl)Methyl]-3,4-Dihydroisoquinolin-1(2H)-One


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 2 of Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-2-[(4-Methoxy-6- Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl)Methyl]-7-[(R)-Methoxy(Oxetan-3- Yl)Methyl]-3,4-Dihydroisoquinolin-1(2H)-One within 5.0Å range: probe atom residue distance (Å) B Occ A:Zn702 b:65.9 occ:0.75 SG A:CYS420 2.4 63.9 1.0 SG A:CYS444 2.5 66.2 1.0 SG A:CYS433 2.6 67.1 1.0 SG A:CYS440 2.6 57.9 1.0 CB A:CYS444 3.3 67.2 1.0 CB A:CYS440 3.3 60.5 1.0 CB A:CYS420 3.4 65.0 1.0 CA A:CYS440 3.6 61.8 1.0 CB A:CYS433 3.6 71.8 1.0 N A:CYS420 3.8 62.9 1.0 ZN A:ZN701 3.8 75.7 0.7 ZN A:ZN703 4.1 77.3 0.8 CA A:CYS420 4.2 65.4 1.0 CA A:CYS444 4.6 66.8 1.0 N A:CYS440 4.6 63.1 1.0 N A:GLU441 4.6 62.9 1.0 C A:CYS440 4.7 62.1 1.0 SG A:CYS446 4.7 69.6 1.0 CE1 A:TYR417 4.8 58.6 1.0 SG A:CYS427 4.8 77.2 1.0 C A:PRO419 4.9 59.9 1.0 SG A:CYS431 4.9 79.9 1.0 OH A:TYR417 5.0 58.6 1.0 O A:CYS420 5.0 68.3 1.0

Zinc binding site 3 out of 14 in the Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-2-[(4-Methoxy-6- Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl)Methyl]-7-[(R)-Methoxy(Oxetan-3- Yl)Methyl]-3,4-Dihydroisoquinolin-1(2H)-One


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 3 of Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-2-[(4-Methoxy-6- Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl)Methyl]-7-[(R)-Methoxy(Oxetan-3- Yl)Methyl]-3,4-Dihydroisoquinolin-1(2H)-One within 5.0Å range: probe atom residue distance (Å) B Occ A:Zn703 b:77.3 occ:0.81 SG A:CYS427 2.3 77.2 1.0 SG A:CYS446 2.4 69.6 1.0 SG A:CYS450 2.5 72.6 1.0 SG A:CYS440 2.6 57.9 1.0 CB A:CYS446 3.2 71.8 1.0 CB A:CYS450 3.3 77.7 1.0 CB A:CYS427 3.5 81.4 1.0 CB A:CYS440 3.6 60.5 1.0 ZN A:ZN701 3.9 75.7 0.7 ZN A:ZN702 4.1 65.9 0.8 SG A:CYS420 4.2 63.9 1.0 CA A:CYS446 4.7 72.6 1.0 CG A:ARG453 4.7 67.2 1.0 CA A:CYS450 4.8 78.8 1.0 CA A:CYS427 4.8 82.5 1.0 NE A:ARG453 4.8 68.1 1.0 CB A:ASN452 4.9 70.7 1.0 NE2 A:HIS422 4.9 81.4 1.0 CB A:CYS444 5.0 67.2 1.0

Zinc binding site 4 out of 14 in the Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-2-[(4-Methoxy-6- Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl)Methyl]-7-[(R)-Methoxy(Oxetan-3- Yl)Methyl]-3,4-Dihydroisoquinolin-1(2H)-One


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 4 of Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-2-[(4-Methoxy-6- Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl)Methyl]-7-[(R)-Methoxy(Oxetan-3- Yl)Methyl]-3,4-Dihydroisoquinolin-1(2H)-One within 5.0Å range: probe atom residue distance (Å) B Occ A:Zn704 b:74.0 occ:0.80 SG A:CYS463 2.3 70.6 1.0 SG A:CYS468 2.4 68.6 1.0 SG A:CYS457 2.6 65.0 1.0 SG A:CYS459 2.6 64.0 1.0 CB A:CYS463 2.9 68.9 1.0 CB A:CYS468 3.3 70.0 1.0 CB A:CYS459 3.4 66.7 1.0 CA A:CYS463 3.5 70.4 1.0 ZN A:ZN705 3.5 65.8 0.8 CB A:CYS457 3.7 64.8 1.0 SG A:CYS477 3.8 58.7 1.0 ZN A:ZN706 4.0 58.8 0.7 N A:CYS463 4.4 71.4 1.0 CA A:CYS468 4.5 70.2 1.0 C A:CYS463 4.5 70.9 1.0 O A:CYS463 4.6 70.8 1.0 CB A:CYS485 4.6 68.6 1.0 CA A:CYS459 4.7 68.5 1.0 SG A:CYS485 4.7 70.5 1.0 N A:CYS459 4.8 68.9 1.0 CB A:CYS470 5.0 62.0 1.0

Zinc binding site 5 out of 14 in the Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-2-[(4-Methoxy-6- Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl)Methyl]-7-[(R)-Methoxy(Oxetan-3- Yl)Methyl]-3,4-Dihydroisoquinolin-1(2H)-One


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 5 of Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-2-[(4-Methoxy-6- Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl)Methyl]-7-[(R)-Methoxy(Oxetan-3- Yl)Methyl]-3,4-Dihydroisoquinolin-1(2H)-One within 5.0Å range: probe atom residue distance (Å) B Occ A:Zn705 b:65.8 occ:0.75 SG A:CYS498 2.3 63.4 1.0 SG A:CYS463 2.4 70.6 1.0 SG A:CYS477 2.5 58.7 1.0 SG A:CYS485 2.6 70.5 1.0 CB A:CYS463 3.1 68.9 1.0 CB A:CYS485 3.4 68.6 1.0 CB A:CYS498 3.4 66.0 1.0 CB A:CYS477 3.5 61.9 1.0 ZN A:ZN704 3.5 74.0 0.8 ZN A:ZN706 4.3 58.8 0.7 SG A:CYS457 4.3 65.0 1.0 CB A:ALA487 4.3 67.8 1.0 CA A:CYS498 4.4 66.2 1.0 CB A:ASN500 4.5 53.6 1.0 CA A:CYS463 4.6 70.4 1.0 CA A:CYS485 4.8 67.3 1.0 O A:GLN462 4.9 72.2 1.0 N A:ASN500 4.9 56.8 1.0 CA A:CYS477 4.9 61.5 1.0

Zinc binding site 6 out of 14 in the Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-2-[(4-Methoxy-6- Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl)Methyl]-7-[(R)-Methoxy(Oxetan-3- Yl)Methyl]-3,4-Dihydroisoquinolin-1(2H)-One


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 6 of Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-2-[(4-Methoxy-6- Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl)Methyl]-7-[(R)-Methoxy(Oxetan-3- Yl)Methyl]-3,4-Dihydroisoquinolin-1(2H)-One within 5.0Å range: probe atom residue distance (Å) B Occ A:Zn706 b:58.8 occ:0.71 SG A:CYS482 2.3 56.2 1.0 SG A:CYS477 2.3 58.7 1.0 SG A:CYS470 2.5 63.3 1.0 SG A:CYS457 2.5 65.0 1.0 CB A:CYS477 3.3 61.9 1.0 CB A:CYS457 3.5 64.8 1.0 CB A:CYS470 3.5 62.0 1.0 CB A:CYS482 3.5 59.9 1.0 N A:CYS457 3.6 65.6 1.0 CA A:CYS477 3.6 61.5 1.0 ZN A:ZN704 4.0 74.0 0.8 CA A:CYS457 4.1 65.8 1.0 C A:GLY456 4.3 65.6 1.0 ZN A:ZN705 4.3 65.8 0.8 N A:ASP478 4.5 61.6 1.0 CA A:GLY456 4.5 65.1 1.0 SG A:CYS468 4.6 68.6 1.0 C A:CYS477 4.6 62.4 1.0 N A:CYS477 4.6 61.6 1.0 O A:CYS457 4.7 66.8 1.0 CA A:CYS482 4.7 59.7 1.0 C A:CYS457 4.8 67.5 1.0 SG A:CYS485 4.8 70.5 1.0 CA A:CYS470 4.9 61.6 1.0

Zinc binding site 7 out of 14 in the Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-2-[(4-Methoxy-6- Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl)Methyl]-7-[(R)-Methoxy(Oxetan-3- Yl)Methyl]-3,4-Dihydroisoquinolin-1(2H)-One


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 7 of Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-2-[(4-Methoxy-6- Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl)Methyl]-7-[(R)-Methoxy(Oxetan-3- Yl)Methyl]-3,4-Dihydroisoquinolin-1(2H)-One within 5.0Å range: probe atom residue distance (Å) B Occ A:Zn707 b:63.8 occ:0.70 ND1 A:HIS285 2.2 61.2 1.0 SG A:CYS277 2.3 62.6 1.0 SG A:CYS282 2.4 55.7 1.0 SG A:CYS274 2.4 57.6 1.0 CG A:HIS285 3.0 63.0 1.0 CE1 A:HIS285 3.2 62.1 1.0 CB A:HIS285 3.2 68.2 1.0 CB A:CYS274 3.3 56.5 1.0 CB A:CYS282 3.3 58.4 1.0 CB A:CYS277 3.7 58.3 1.0 N A:HIS285 3.9 68.5 1.0 N A:CYS277 4.1 54.1 1.0 CA A:HIS285 4.2 71.3 1.0 CB A:LEU284 4.2 65.2 1.0 CD2 A:HIS285 4.2 61.6 1.0 NE2 A:HIS285 4.3 62.5 1.0 CB A:ARG276 4.4 53.7 1.0 CA A:CYS277 4.5 54.9 1.0 N A:LEU284 4.5 62.6 1.0 C A:LEU284 4.6 66.2 1.0 CA A:LEU284 4.7 64.1 1.0 CA A:CYS282 4.7 60.2 1.0 CA A:CYS274 4.8 56.1 1.0 C A:ARG276 4.8 55.0 1.0

Zinc binding site 8 out of 14 in the Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-2-[(4-Methoxy-6- Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl)Methyl]-7-[(R)-Methoxy(Oxetan-3- Yl)Methyl]-3,4-Dihydroisoquinolin-1(2H)-One


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 8 of Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-2-[(4-Methoxy-6- Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl)Methyl]-7-[(R)-Methoxy(Oxetan-3- Yl)Methyl]-3,4-Dihydroisoquinolin-1(2H)-One within 5.0Å range: probe atom residue distance (Å) B Occ B:Zn701 b:78.4 occ:0.65 SG B:CYS446 2.3 76.9 1.0 SG B:CYS427 2.4 83.1 1.0 SG B:CYS450 2.5 75.8 1.0 SG B:CYS440 2.8 70.4 1.0 CB B:CYS446 3.2 73.6 1.0 CB B:CYS450 3.3 79.4 1.0 ZN B:ZN703 3.6 72.8 0.6 CB B:CYS427 3.6 86.0 1.0 CB B:CYS440 3.6 67.2 1.0 ZN B:ZN702 4.0 71.6 0.8 SG B:CYS420 4.3 72.7 1.0 CA B:CYS446 4.6 74.8 1.0 CG B:ARG453 4.7 68.8 1.0 CA B:CYS450 4.7 80.3 1.0 NE B:ARG453 4.9 68.6 1.0 NE2 B:HIS422 4.9 84.4 1.0 CB B:ASN452 4.9 72.9 1.0 CB B:CYS444 4.9 71.1 1.0 CA B:CYS427 4.9 87.0 1.0

Zinc binding site 9 out of 14 in the Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-2-[(4-Methoxy-6- Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl)Methyl]-7-[(R)-Methoxy(Oxetan-3- Yl)Methyl]-3,4-Dihydroisoquinolin-1(2H)-One


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 9 of Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-2-[(4-Methoxy-6- Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl)Methyl]-7-[(R)-Methoxy(Oxetan-3- Yl)Methyl]-3,4-Dihydroisoquinolin-1(2H)-One within 5.0Å range: probe atom residue distance (Å) B Occ B:Zn702 b:71.6 occ:0.81 SG B:CYS440 2.5 70.4 1.0 SG B:CYS433 2.5 70.2 1.0 SG B:CYS444 2.5 70.4 1.0 SG B:CYS420 2.6 72.7 1.0 CB B:CYS440 3.2 67.2 1.0 CB B:CYS420 3.3 71.1 1.0 CB B:CYS444 3.4 71.1 1.0 ZN B:ZN703 3.5 72.8 0.6 CB B:CYS433 3.5 73.9 1.0 CA B:CYS440 3.7 65.6 1.0 N B:CYS420 3.8 69.7 1.0 ZN B:ZN701 4.0 78.4 0.7 CA B:CYS420 4.2 71.4 1.0 SG B:CYS446 4.6 76.9 1.0 N B:CYS440 4.6 65.7 1.0 SG B:CYS431 4.6 83.0 1.0 CA B:CYS444 4.7 71.3 1.0 C B:CYS440 4.8 64.6 1.0 N B:GLU441 4.8 64.3 1.0 SG B:CYS427 4.8 83.1 1.0 CA B:CYS433 4.9 76.6 1.0 CE1 B:TYR417 5.0 59.6 1.0 C B:PRO419 5.0 67.8 1.0 O B:CYS420 5.0 73.2 1.0 C B:CYS420 5.0 73.8 1.0 O B:GLN418 5.0 64.9 1.0

Zinc binding site 10 out of 14 in the Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-2-[(4-Methoxy-6- Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl)Methyl]-7-[(R)-Methoxy(Oxetan-3- Yl)Methyl]-3,4-Dihydroisoquinolin-1(2H)-One


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 10 of Structure of Hs/ACPRC2 in Complex with 5,8-Dichloro-2-[(4-Methoxy-6- Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl)Methyl]-7-[(R)-Methoxy(Oxetan-3- Yl)Methyl]-3,4-Dihydroisoquinolin-1(2H)-One within 5.0Å range: probe atom residue distance (Å) B Occ B:Zn703 b:72.8 occ:0.59 SG B:CYS420 2.3 72.7 1.0 NE2 B:HIS422 2.4 84.4 1.0 SG B:CYS427 2.5 83.1 1.0 SG B:CYS431 2.5 83.0 1.0 CE1 B:HIS422 3.2 84.6 1.0 CB B:CYS420 3.2 71.1 1.0 CD2 B:HIS422 3.3 84.2 1.0 ZN B:ZN702 3.5 71.6 0.8 ZN B:ZN701 3.6 78.4 0.7 CB B:CYS427 3.7 86.0 1.0 CB B:CYS431 3.9 83.6 1.0 SG B:CYS440 4.0 70.4 1.0 ND1 B:HIS422 4.2 84.9 1.0 CG B:HIS422 4.3 84.9 1.0 CA B:CYS427 4.3 87.0 1.0 CB B:CYS446 4.5 73.6 1.0 CA B:CYS420 4.6 71.4 1.0 SG B:CYS433 4.7 70.2 1.0 SG B:CYS446 4.7 76.9 1.0 CD B:PRO432 4.8 80.3 1.0 CB B:CYS433 4.9 73.9 1.0 CA B:CYS431 4.9 83.3 1.0 C B:CYS420 4.9 73.8 1.0 N B:CYS427 5.0 88.0 1.0

P.P.Kung, P.Bingham, A.Brooun, M.Collins, Y.L.Deng, D.Dinh, C.Fan, K.S.Gajiwala, R.Grantner, H.J.Gukasyan, W.Hu, B.Huang, R.Kania, S.E.Kephart, C.Krivacic, R.A.Kumpf, P.Khamphavong, M.Kraus, W.Liu, K.A.Maegley, L.Nguyen, S.Ren, D.Richter, R.A.Rollins, N.Sach, S.Sharma, J.Sherrill, J.Spangler, A.E.Stewart, S.Sutton, S.Uryu, D.Verhelle, H.Wang, S.Wang, M.Wythes, S.Xin, S.Yamazaki, H.Zhu, J.Zhu, L.Zehnder, M.Edwards. Optimization of Orally Bioavailable Enhancer of Zeste Homolog 2 (EZH2) Inhibitors Using Ligand and Property-Based Design Strategies: Identification of Development Candidate (R)-5,8-Dichloro-7-(Methoxy(Oxetan-3-Yl)Methyl) -2-((4-Methoxy-6-Methyl-2-Oxo-1,2-Dihydropyridin-3-Yl) Methyl)-3,4-Dihydroisoquinolin-1(2H)-One (Pf-06821497). J. Med. Chem. V. 61 650 2018.
ISSN: ISSN 1520-4804
PubMed: 29211475
DOI: 10.1021/ACS.JMEDCHEM.7B01375