Zinc in PDB 5v9t: Crystal Structure of Selective Pyrrolidine Amide KDM5A Inhibitor N- {(3R)-1-[3-(Propan-2-Yl)-1H-Pyrazole-5-Carbonyl]Pyrrolidin-3- Yl}Cyclopropanecarboxamide (Compound 48)

The structure of Crystal Structure of Selective Pyrrolidine Amide KDM5A Inhibitor N- {(3R)-1-[3-(Propan-2-Yl)-1H-Pyrazole-5-Carbonyl]Pyrrolidin-3- Yl}Cyclopropanecarboxamide (Compound 48), PDB code: 5v9t was solved by J.R.Kiefer, J.Liang, M.Vinogradova, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	34.54 / 3.05
Space group	P 31
Cell size a, b, c (Å), α, β, γ (°)	159.615, 159.615, 92.071, 90.00, 90.00, 120.00
R / Rfree (%)	23.2 / 29

The structure of Crystal Structure of Selective Pyrrolidine Amide KDM5A Inhibitor N- {(3R)-1-[3-(Propan-2-Yl)-1H-Pyrazole-5-Carbonyl]Pyrrolidin-3- Yl}Cyclopropanecarboxamide (Compound 48) also contains other interesting chemical elements:

Nickel

(Ni)

2 atoms

The binding sites of Zinc atom in the Crystal Structure of Selective Pyrrolidine Amide KDM5A Inhibitor N- {(3R)-1-[3-(Propan-2-Yl)-1H-Pyrazole-5-Carbonyl]Pyrrolidin-3- Yl}Cyclopropanecarboxamide (Compound 48) (pdb code 5v9t). This binding sites where shown within 5.0 Angstroms radius around Zinc atom.
In total 4 binding sites of Zinc where determined in the Crystal Structure of Selective Pyrrolidine Amide KDM5A Inhibitor N- {(3R)-1-[3-(Propan-2-Yl)-1H-Pyrazole-5-Carbonyl]Pyrrolidin-3- Yl}Cyclopropanecarboxamide (Compound 48), PDB code: 5v9t:
Jump to Zinc binding site number: 1; 2; 3; 4;

Zinc binding site 1 out of 4 in the Crystal Structure of Selective Pyrrolidine Amide KDM5A Inhibitor N- {(3R)-1-[3-(Propan-2-Yl)-1H-Pyrazole-5-Carbonyl]Pyrrolidin-3- Yl}Cyclopropanecarboxamide (Compound 48)


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 Selective Pyrrolidine Amide KDM5A Inhibitor N- {(3R)-1-[3-(Propan-2-Yl)-1H-Pyrazole-5-Carbonyl]Pyrrolidin-3- Yl}Cyclopropanecarboxamide (Compound 48) within 5.0Å range: probe atom residue distance (Å) B Occ A:Zn902 b:0.1 occ:1.01 HB3 A:CYS699 1.6 0.9 1.0 HB2 A:CYS679 2.1 0.4 1.0 SG A:CYS679 2.1 91.2 1.0 SG A:CYS676 2.1 92.0 1.0 H A:CYS699 2.2 0.3 1.0 CB A:CYS699 2.2 85.1 1.0 HB2 A:CYS676 2.3 0.8 1.0 SG A:CYS699 2.3 87.1 1.0 CB A:CYS676 2.5 89.1 1.0 CB A:CYS679 2.5 94.7 1.0 HB3 A:CYS676 2.5 0.8 1.0 N A:CYS699 2.9 97.9 1.0 HB2 A:CYS699 3.0 0.9 1.0 CA A:CYS699 3.1 92.0 1.0 HB3 A:CYS679 3.1 0.4 1.0 H A:THR681 3.6 0.1 1.0 CA A:CYS679 3.6 92.4 1.0 HB2 A:HIS702 3.7 1.0 1.0 HA A:CYS699 3.7 0.3 1.0 HA A:CYS679 3.8 0.7 1.0 N A:CYS679 3.9 94.1 1.0 HG22 A:VAL698 3.9 1.0 1.0 CA A:CYS676 4.0 89.3 1.0 O A:ALA678 4.0 0.0 1.0 HB A:THR681 4.0 0.8 1.0 HA A:VAL698 4.1 0.5 1.0 C A:VAL698 4.1 88.5 1.0 C A:CYS699 4.1 87.2 1.0 H A:CYS679 4.1 0.8 1.0 C A:ALA678 4.2 99.4 1.0 HA A:ARG680 4.3 0.9 1.0 HA A:CYS676 4.3 1.0 1.0 H A:HIS702 4.4 0.5 1.0 O A:CYS699 4.4 89.5 1.0 H A:CYS676 4.4 1.0 1.0 N A:THR681 4.4 0.5 1.0 ND1 A:HIS702 4.5 0.6 1.0 CB A:HIS702 4.5 0.3 1.0 HG23 A:VAL698 4.6 1.0 1.0 CG A:HIS702 4.6 0.6 1.0 CA A:VAL698 4.6 90.5 1.0 CG2 A:VAL698 4.7 0.1 1.0 C A:CYS676 4.7 91.3 1.0 H A:ALA678 4.7 0.1 1.0 N A:CYS676 4.7 95.9 1.0 HB2 A:TYR701 4.8 0.5 1.0 H A:TYR701 4.8 0.1 1.0 CB A:THR681 4.8 0.8 1.0 C A:CYS679 4.9 92.4 1.0 N A:HIS702 4.9 0.7 1.0 OG1 A:THR681 4.9 0.5 1.0 HG A:CYS683 5.0 0.3 1.0

Zinc binding site 2 out of 4 in the Crystal Structure of Selective Pyrrolidine Amide KDM5A Inhibitor N- {(3R)-1-[3-(Propan-2-Yl)-1H-Pyrazole-5-Carbonyl]Pyrrolidin-3- Yl}Cyclopropanecarboxamide (Compound 48)


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 Selective Pyrrolidine Amide KDM5A Inhibitor N- {(3R)-1-[3-(Propan-2-Yl)-1H-Pyrazole-5-Carbonyl]Pyrrolidin-3- Yl}Cyclopropanecarboxamide (Compound 48) within 5.0Å range: probe atom residue distance (Å) B Occ A:Zn903 b:0.2 occ:1.01 H A:CYS692 1.8 1.0 1.0 HB3 A:CYS692 1.9 0.5 1.0 HG A:CYS690 2.2 0.0 1.0 HB3 A:CYS690 2.3 0.4 1.0 CB A:CYS692 2.3 0.1 1.0 SG A:CYS690 2.4 0.0 1.0 N A:CYS692 2.4 0.6 1.0 SG A:CYS709 2.5 0.7 1.0 SG A:CYS692 2.5 0.7 1.0 CB A:CYS690 2.8 0.8 1.0 CA A:CYS692 2.8 0.7 1.0 HB2 A:CYS709 3.1 0.4 1.0 HA A:CYS692 3.1 0.8 1.0 HB3 A:CYS709 3.2 0.4 1.0 CB A:CYS709 3.2 0.1 1.0 HB2 A:CYS692 3.2 0.5 1.0 H A:SER691 3.3 0.0 1.0 HB2 A:CYS690 3.4 0.4 1.0 N A:SER691 3.5 0.6 1.0 C A:SER691 3.6 0.6 1.0 HB3 A:CYS707 3.8 0.6 1.0 C A:CYS690 3.8 1.0 1.0 CA A:CYS690 3.9 0.7 1.0 CA A:SER691 4.1 0.7 1.0 C A:CYS692 4.2 0.2 1.0 H A:ASN693 4.3 0.6 1.0 SG A:CYS707 4.3 0.7 1.0 HG A:CYS707 4.3 0.3 1.0 HB2 A:SER691 4.4 0.7 1.0 CB A:CYS707 4.5 0.4 1.0 HA A:CYS690 4.5 0.8 1.0 O A:SER691 4.6 0.4 1.0 N A:ASN693 4.6 0.3 1.0 CA A:CYS709 4.6 0.3 1.0 O A:CYS690 4.7 0.6 1.0 H A:CYS690 4.7 0.1 1.0 H A:CYS709 4.7 0.1 1.0 HB2 A:CYS707 4.8 0.6 1.0 CB A:SER691 4.9 0.9 1.0 N A:CYS690 4.9 0.4 1.0 HA A:SER691 4.9 0.2 1.0 HD22 A:LEU706 4.9 0.0 1.0

Zinc binding site 3 out of 4 in the Crystal Structure of Selective Pyrrolidine Amide KDM5A Inhibitor N- {(3R)-1-[3-(Propan-2-Yl)-1H-Pyrazole-5-Carbonyl]Pyrrolidin-3- Yl}Cyclopropanecarboxamide (Compound 48)


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 Selective Pyrrolidine Amide KDM5A Inhibitor N- {(3R)-1-[3-(Propan-2-Yl)-1H-Pyrazole-5-Carbonyl]Pyrrolidin-3- Yl}Cyclopropanecarboxamide (Compound 48) within 5.0Å range: probe atom residue distance (Å) B Occ B:Zn902 b:0.4 occ:1.00 HB3 B:CYS699 1.8 96.0 1.0 HB2 B:CYS679 1.9 0.5 1.0 SG B:CYS679 1.9 88.8 1.0 SG B:CYS676 2.1 87.2 1.0 SG B:CYS699 2.2 81.1 1.0 CB B:CYS679 2.3 0.1 1.0 CB B:CYS699 2.3 80.2 1.0 H B:CYS699 2.4 0.1 1.0 HB2 B:CYS676 2.5 94.6 1.0 HB3 B:CYS676 2.5 94.6 1.0 CB B:CYS676 2.5 79.0 1.0 HB3 B:CYS679 3.0 0.5 1.0 HB2 B:CYS699 3.1 96.0 1.0 N B:CYS699 3.1 83.6 1.0 CA B:CYS699 3.3 82.8 1.0 H B:THR681 3.4 0.2 1.0 CA B:CYS679 3.5 76.4 1.0 HA B:CYS679 3.6 91.5 1.0 N B:CYS679 3.7 89.3 1.0 HB2 B:HIS702 3.7 0.6 1.0 HB B:THR681 3.9 0.8 1.0 O B:ALA678 3.9 0.7 1.0 HA B:CYS699 3.9 99.2 1.0 H B:CYS679 4.0 1.0 1.0 CA B:CYS676 4.0 79.4 1.0 C B:ALA678 4.1 0.5 1.0 HG22 B:VAL698 4.1 0.6 1.0 HA B:ARG680 4.2 86.6 1.0 HA B:VAL698 4.2 0.8 1.0 N B:THR681 4.3 97.0 1.0 C B:CYS699 4.3 85.3 1.0 C B:VAL698 4.4 85.6 1.0 HA B:CYS676 4.4 95.2 1.0 OG1 B:THR681 4.4 0.5 1.0 H B:CYS676 4.5 92.4 1.0 HG1 B:THR681 4.5 0.5 1.0 H B:HIS702 4.5 0.3 1.0 O B:CYS699 4.5 87.2 1.0 CG B:HIS702 4.6 0.4 1.0 CB B:THR681 4.6 0.8 1.0 CB B:HIS702 4.6 0.5 1.0 ND1 B:HIS702 4.6 0.2 1.0 C B:CYS676 4.7 79.9 1.0 H B:ALA678 4.7 0.7 1.0 C B:CYS679 4.7 90.5 1.0 N B:CYS676 4.8 77.2 1.0 HG23 B:VAL698 4.8 0.6 1.0 CA B:VAL698 4.8 86.6 1.0 HB2 B:TYR701 4.8 0.3 1.0 CG2 B:VAL698 4.9 0.2 1.0 H B:TYR701 4.9 0.0 1.0 CA B:ARG680 5.0 72.3 1.0 HD3 B:ARG603 5.0 0.8 1.0

Zinc binding site 4 out of 4 in the Crystal Structure of Selective Pyrrolidine Amide KDM5A Inhibitor N- {(3R)-1-[3-(Propan-2-Yl)-1H-Pyrazole-5-Carbonyl]Pyrrolidin-3- Yl}Cyclopropanecarboxamide (Compound 48)


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 Selective Pyrrolidine Amide KDM5A Inhibitor N- {(3R)-1-[3-(Propan-2-Yl)-1H-Pyrazole-5-Carbonyl]Pyrrolidin-3- Yl}Cyclopropanecarboxamide (Compound 48) within 5.0Å range: probe atom residue distance (Å) B Occ B:Zn903 b:0.1 occ:1.00 HB3 B:CYS692 1.7 0.7 1.0 H B:CYS692 2.2 0.4 1.0 HG B:CYS690 2.2 0.6 1.0 CB B:CYS692 2.4 0.2 1.0 SG B:CYS709 2.4 0.7 1.0 HB3 B:CYS709 2.4 0.5 1.0 HB2 B:CYS709 2.6 0.5 1.0 SG B:CYS690 2.6 0.5 1.0 CB B:CYS709 2.6 0.0 1.0 N B:CYS692 2.8 0.5 1.0 HB3 B:CYS690 2.8 0.8 1.0 SG B:CYS692 2.8 0.8 1.0 CA B:CYS692 3.0 0.3 1.0 HA B:CYS692 3.2 0.4 1.0 HB2 B:CYS692 3.2 0.7 1.0 CB B:CYS690 3.3 0.3 1.0 H B:SER691 3.8 0.8 1.0 HB3 B:CYS707 3.8 0.5 1.0 HB2 B:CYS690 3.9 0.8 1.0 C B:SER691 3.9 0.3 1.0 N B:SER691 4.0 0.3 1.0 SG B:CYS707 4.1 0.5 1.0 CA B:CYS709 4.1 0.4 1.0 H B:CYS709 4.3 0.2 1.0 C B:CYS690 4.3 0.2 1.0 CA B:CYS690 4.4 0.7 1.0 CB B:CYS707 4.4 0.7 1.0 C B:CYS692 4.4 0.0 1.0 CA B:SER691 4.5 0.8 1.0 HA B:CYS709 4.6 0.3 1.0 H B:ASN693 4.6 0.2 1.0 HB2 B:SER691 4.7 0.4 1.0 N B:CYS709 4.7 0.6 1.0 HB2 B:CYS707 4.8 0.5 1.0 O B:SER691 4.9 0.6 1.0 C B:CYS709 4.9 0.9 1.0 N B:ASN693 4.9 0.2 1.0 HA B:CYS690 4.9 0.5 1.0 O B:CYS709 5.0 0.3 1.0

J.Liang, S.Labadie, B.Zhang, D.F.Ortwine, S.Patel, M.Vinogradova, J.R.Kiefer, T.Mauer, V.S.Gehling, J.C.Harmange, R.Cummings, T.Lai, J.Liao, X.Zheng, Y.Liu, A.Gustafson, E.Van Der Porten, W.Mao, B.M.Liederer, G.Deshmukh, L.An, Y.Ran, M.Classon, P.Trojer, P.S.Dragovich, L.Murray. From A Novel Hts Hit to Potent, Selective, and Orally Bioavailable KDM5 Inhibitors. Bioorg. Med. Chem. Lett. V. 27 2974 2017.
ISSN: ESSN 1464-3405
PubMed: 28512031
DOI: 10.1016/J.BMCL.2017.05.016