PDBsum entry 3dbf

Transferase

PDB id: 3dbf

Contents

Protein chain

261 a.a. *

Ligands

5FR

Waters ×4

* Residue conservation analysis

PDB id:

3dbf

Name:

Transferase

Title:

Crystal structure of an activated (thr->asp) polo-like kinase 1 (plk1) catalytic domain in complex with compound 562

Structure:

Polo-like kinase. Chain: a. Fragment: plk1 kinase domain. Engineered: yes. Mutation: yes

Source:

Danio rerio. Zebrafish. Organism_taxid: 7955. Gene: plk1. Expressed in: escherichia coli.

Resolution:

3.20Å R-factor: 0.234 R-free: 0.275

Authors:

R.A.Elling,J.Zhu,K.J.Barr,M.J.Romanowski

Key ref:

R.V.Fucini et al. (2008). Design and synthesis of 2-amino-pyrazolopyridines as Polo-like kinase 1 inhibitors. Bioorg Med Chem Lett, 18, 5648-5652. PubMed id: 18793847

Date:

31-May-08 Release date: 07-Oct-08

Protein chain

Q4KMI8  (Q4KMI8_DANRE) -  Serine/threonine-protein kinase PLK from Danio rerio

Seq: 595 a.a.

Struc: 261 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.11.21 - polo 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

Bioorg Med Chem Lett 18:5648-5652 (2008)

PubMed id: 18793847

Design and synthesis of 2-amino-pyrazolopyridines as Polo-like kinase 1 inhibitors.

R.V.Fucini, E.J.Hanan, M.J.Romanowski, R.A.Elling, W.Lew, K.J.Barr, J.Zhu, J.C.Yoburn, Y.Liu, B.T.Fahr, J.Fan, Y.Lu, P.Pham, I.C.Choong, E.C.VanderPorten, M.Bui, H.E.Purkey, M.J.Evanchik, W.Yang.

ABSTRACT

A series of 2-amino-pyrazolopyridines was designed and synthesized as Polo-like kinase (Plk) inhibitors based on a low micromolar hit. The SAR was developed to provide compounds exhibiting low nanomolar inhibitory activity of Plk1; the phenotype of treated cells is consistent with Plk1 inhibition. A co-crystal structure of one of these compounds with zPlk1 confirms an ATP-competitive binding mode.