PDBsum entry 2f7x

Transferase

PDB id: 2f7x

Contents

Protein chains

336 a.a. *

20 a.a. *

Ligands

4EA

Waters ×195

* Residue conservation analysis

PDB id:

2f7x

Name:

Transferase

Title:

Protein kinase a bound to (s)-2-(1h-indol-3-yl)-1-[5-((e)-2-pyridin-4- yl-vinyl)-pyridin-3-yloxymethyl]-ethylamine

Structure:

Camp-dependent protein kinase, alpha-catalytic subunit. Chain: e. Synonym: pka c-alpha. Engineered: yes. Pki, inhibitory peptide. Chain: i. Engineered: yes

Source:

Bos taurus. Cattle. Organism_taxid: 9913. Gene: prkaca. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes

Biol. unit:

Dimer (from PQS)

Resolution:

1.90Å R-factor: 0.268 R-free: 0.297

Authors:

Q.Li,T.Li,G.D.Zhu,J.Gong,A.Claibone,C.Dalton,Y.Luo,E.F.Johnson,Y.Shi, X.Liu,V.Klinghofer,J.L.Bauch,K.C.Marsh,J.J.Bouska,S.Arries,R.De Jong,T.Oltersdorf,V.S.Stoll,C.G.Jakob,S.H.Rosenberg,V.L.Giranda

Key ref:

Q.Li et al. (2006). Discovery of trans-3,4'-bispyridinylethylenes as potent and novel inhibitors of protein kinase B (PKB/Akt) for the treatment of cancer: Synthesis and biological evaluation. Bioorg Med Chem Lett, 16, 1679-1685. PubMed id: 16403626 DOI: 10.1016/j.bmcl.2005.12.017

Date:

01-Dec-05 Release date: 27-Jun-06

Protein chain

P00517  (KAPCA_BOVIN) -  cAMP-dependent protein kinase catalytic subunit alpha from Bos taurus

Seq: 351 a.a.

Struc: 336 a.a.

Protein chain

Q71U53  (IPKA_PIG) -  cAMP-dependent protein kinase inhibitor alpha from Sus scrofa

Seq: 76 a.a.

Struc: 20 a.a.

Enzyme reactions

• Enzyme class 2: Chain E: E.C.2.7.11.11 - cAMP-dependent 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⁺
• Enzyme class 3: Chain I: E.C.?

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

reference

DOI no: 10.1016/j.bmcl.2005.12.017

Bioorg Med Chem Lett 16:1679-1685 (2006)

PubMed id: 16403626

Discovery of trans-3,4'-bispyridinylethylenes as potent and novel inhibitors of protein kinase B (PKB/Akt) for the treatment of cancer: Synthesis and biological evaluation.

Q.Li, T.Li, G.D.Zhu, J.Gong, A.Claibone, C.Dalton, Y.Luo, E.F.Johnson, Y.Shi, X.Liu, V.Klinghofer, J.L.Bauch, K.C.Marsh, J.J.Bouska, S.Arries, R.De Jong, T.Oltersdorf, V.S.Stoll, C.G.Jakob, S.H.Rosenberg, V.L.Giranda.

ABSTRACT

A novel series of Akt/PKB inhibitors derived from a screening lead (1) has been prepared. The novel trans-3,4'-bispyridinylethylenes described herein are potent inhibitors of Akt/PKB with IC(50) values in the low double-digit nanomolar range against Akt1. Compound 2q shows excellent selectivity against distinct families of kinases such as tyrosine kinases and CAMK, and displays poor to modest selectivity against closely related kinases in the AGC and CMGC families. The cellular activities including inhibition of cell growth and phosphorylation of downstream target GSK3 are also described. The X-ray structure of compound 2q complexed with PKA in the ATP binding site was determined.