Zinc in PDB 2obq: Discovery of the Hcv NS3/4A Protease Inhibitor SCH503034. Key Steps in Structure-Based Optimization

The structure of Discovery of the Hcv NS3/4A Protease Inhibitor SCH503034. Key Steps in Structure-Based Optimization, PDB code: 2obq was solved by A.J.Prongay, Z.Guo, N.Yao, T.Fischmann, C.Strickland, J.Myers Jr., P.C.Weber, B.Malcolm, B.M.Beyer, R.Ingram, J.Pichardo, Z.Hong, W.W.Prosise, L.Ramanathan, S.S.Taremi, T.Yarosh-Tomaine, R.Zhang, M.Senior, R.Yang, A.Arasappan, F.Bennett, S.F.Bogen, K.Chen, E.Jao, Y.Liu, R.G.Love, A.K.Saksena, S.Venkatraman, V.Girijavallabhan, F.G.Njoroge, V.Madison, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	8.00 / 2.50
Space group	H 3 2
Cell size a, b, c (Å), α, β, γ (°)	225.570, 225.570, 75.720, 90.00, 90.00, 120.00
R / Rfree (%)	20.3 / 26.4

The binding sites of Zinc atom in the Discovery of the Hcv NS3/4A Protease Inhibitor SCH503034. Key Steps in Structure-Based Optimization (pdb code 2obq). This binding sites where shown within 5.0 Angstroms radius around Zinc atom.
In total 2 binding sites of Zinc where determined in the Discovery of the Hcv NS3/4A Protease Inhibitor SCH503034. Key Steps in Structure-Based Optimization, PDB code: 2obq:
Jump to Zinc binding site number: 1; 2;

Zinc binding site 1 out of 2 in the Discovery of the Hcv NS3/4A Protease Inhibitor SCH503034. Key Steps in Structure-Based Optimization


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 1 of Discovery of the Hcv NS3/4A Protease Inhibitor SCH503034. Key Steps in Structure-Based Optimization within 5.0Å range: probe atom residue distance (Å) B Occ A:Zn901 b:35.6 occ:1.00 O A:HOH902 1.8 2.0 1.0 SG A:CYS97 2.2 28.6 1.0 SG A:CYS145 2.2 34.5 1.0 SG A:CYS99 2.3 36.8 1.0 CB A:CYS145 3.3 35.5 1.0 CB A:CYS99 3.4 37.6 1.0 CB A:CYS97 3.5 24.6 1.0 N A:THR98 3.7 44.8 1.0 N A:CYS99 3.7 44.9 1.0 CA A:CYS97 3.8 31.6 1.0 CA A:CYS99 4.1 40.6 1.0 CB A:HIS149 4.2 22.8 1.0 C A:CYS97 4.3 39.6 1.0 C A:THR98 4.4 47.1 1.0 CB A:ALA147 4.5 22.1 1.0 CG A:HIS149 4.7 29.9 1.0 CA A:THR98 4.7 46.3 1.0 CA A:CYS145 4.8 31.1 1.0 ND1 A:HIS149 4.8 35.1 1.0 C A:CYS99 4.8 44.4 1.0 N A:GLY100 5.0 43.7 1.0

Zinc binding site 2 out of 2 in the Discovery of the Hcv NS3/4A Protease Inhibitor SCH503034. Key Steps in Structure-Based Optimization


Mono view


Stereo pair view

A full contact list of Zinc with other atoms in the Zn binding site number 2 of Discovery of the Hcv NS3/4A Protease Inhibitor SCH503034. Key Steps in Structure-Based Optimization within 5.0Å range: probe atom residue distance (Å) B Occ C:Zn902 b:33.1 occ:1.00 SG C:CYS97 2.1 31.3 1.0 O C:HOH903 2.1 2.0 1.0 SG C:CYS145 2.1 30.3 1.0 SG C:CYS99 2.2 36.8 1.0 CB C:CYS145 3.2 27.6 1.0 CB C:CYS97 3.4 32.6 1.0 CB C:CYS99 3.6 41.3 1.0 N C:CYS99 3.7 44.2 1.0 CA C:CYS97 3.8 32.2 1.0 N C:THR98 3.8 37.6 1.0 CA C:CYS99 4.2 42.7 1.0 C C:CYS97 4.3 33.1 1.0 CB C:HIS149 4.3 13.5 1.0 CB C:ALA147 4.5 13.9 1.0 CA C:CYS145 4.6 20.3 1.0 N C:GLY100 4.7 39.4 1.0 C C:THR98 4.7 43.3 1.0 ND1 C:HIS149 4.8 16.5 1.0 CG C:HIS149 4.8 14.5 1.0 C C:CYS99 4.8 43.5 1.0 CA C:THR98 4.9 39.1 1.0 N C:ALA147 4.9 24.2 1.0 CD C:PRO146 5.0 19.1 1.0

A.J.Prongay, Z.Guo, N.Yao, J.Pichardo, T.Fischmann, C.Strickland, J.Myers Jr., P.C.Weber, B.M.Beyer, R.Ingram, Z.Hong, W.W.Prosise, L.Ramanathan, S.S.Taremi, T.Yarosh-Tomaine, R.Zhang, M.Senior, R.S.Yang, B.Malcolm, A.Arasappan, F.Bennett, S.L.Bogen, K.Chen, E.Jao, Y.T.Liu, R.G.Lovey, A.K.Saksena, S.Venkatraman, V.Girijavallabhan, F.G.Njoroge, V.Madison. Discovery of the Hcv NS3/4A Protease Inhibitor (1R,5S)-N-[3-Amino-1-(Cyclobutylmethyl)-2,3-Dioxopropyl]-3- [2(S)-[[[(1,1-Dimethylethyl)Amino]Carbonyl]Amino]-3, 3-Dimethyl-1-Oxobutyl]- 6,6-Dimethyl-3-Azabicyclo[3.1.0]Hexan-2(S)-Carboxamide (Sch 503034) II. Key Steps in Structure-Based Optimization. J.Med.Chem. V. 50 2310 2007.
ISSN: ISSN 0022-2623
PubMed: 17444623
DOI: 10.1021/JM060173K