PDBsum entry 3dcv

Transferase

PDB id: 3dcv

Contents

Protein chain

274 a.a. *

Ligands

55E

Waters ×98

* Residue conservation analysis

PDB id:

3dcv

Name:

Transferase

Title:

Crystal structure of human pim1 kinase complexed with 4-(4-hydroxy-3- methyl-phenyl)-6-phenylpyrimidin-2(1h)-one

Structure:

Proto-oncogene serine/threonine-protein kinase pim-1. Chain: a. Fragment: kinase domain: residues 93-404. Engineered: yes

Source:

Homo sapiens. Organism_taxid: 9606. Gene: pim1. Expressed in: escherichia coli.

Resolution:

2.70Å R-factor: 0.182 R-free: 0.234

Authors:

C.R.Bellamacina,C.M.Shafer,M.Lindvall,T.G.Gesner,A.Yabannavar, J.Weiping,L.Song,A.Walter

Key ref:

C.M.Shafer et al. (2008). 4-(1H-indazol-5-yl)-6-phenylpyrimidin-2(1H)-one analogs as potent CDC7 inhibitors. Bioorg Med Chem Lett, 18, 4482-4485. PubMed id: 18672368 DOI: 10.1016/j.bmcl.2008.07.061

Date:

04-Jun-08 Release date: 19-Aug-08

Protein chain

P11309  (PIM1_HUMAN) -  Serine/threonine-protein kinase pim-1 from Homo sapiens

Seq: 313 a.a.

Struc: 274 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.11.1 - non-specific serine/threonine protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.bmcl.2008.07.061

Bioorg Med Chem Lett 18:4482-4485 (2008)

PubMed id: 18672368

4-(1H-indazol-5-yl)-6-phenylpyrimidin-2(1H)-one analogs as potent CDC7 inhibitors.

C.M.Shafer, M.Lindvall, C.Bellamacina, T.G.Gesner, A.Yabannavar, W.Jia, S.Lin, A.Walter.

ABSTRACT

A series of 4-(4-hydroxyphenyl)-6-phenylpyrimidin-2(1H)-ones were identified by HTS as inhibitors of CDC7. Molecular modeling and medicinal chemistry techniques were employed to explore the SAR for this series with a focus on removing potential metabolic liabilities and improving cellular potency.