spacer
spacer

PDBsum entry 2pe0
Go to PDB code: 
protein ligands links
Transferase PDB id
2pe0

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chain
276 a.a. *
Ligands
SO4 ×2
39Z
GOL ×3
Waters ×49
* Residue conservation analysis
PDB id:
2pe0
Name: Transferase
Title: Crystal structure of human phosphoinositide-dependent protein kinase 1 (pdk1) 5-hydroxy-3-[1-(1h-pyrrol-2-yl)-eth-(z)-ylidene]-1,3-dihydro- indol-2-one complex
Structure: 3-phosphoinositide-dependent protein kinase 1. Chain: a. Fragment: kinase domain. Synonym: hpdk1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: pdpk1, pdk1. Expressed in: unidentified baculovirus. Expression_system_taxid: 10469.
Resolution:
2.35Å     R-factor:   0.202     R-free:   0.240
Authors: M.Whitlow,M.Adler
Key ref: I.Islam et al. (2007). Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 1: design, synthesis and biological activity. Bioorg Med Chem Lett, 17, 3814-3818. PubMed id: 17531483 DOI: 10.1016/j.bmcl.2007.04.071
Date:
01-Apr-07     Release date:   12-Jun-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
O15530  (PDPK1_HUMAN) -  3-phosphoinositide-dependent protein kinase 1 from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		556 a.a.
276 a.a.
Key:    Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.7.11.1  - non-specific serine/threonine protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      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+
L-seryl-[protein]
 + ATP
 = O-phospho-L-seryl-[protein]
 + ADP
 + H(+)
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.2007.04.071 Bioorg Med Chem Lett 17:3814-3818 (2007)
PubMed id: 17531483  
 
 
Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 1: design, synthesis and biological activity.
I.Islam, J.Bryant, Y.L.Chou, M.J.Kochanny, W.Lee, G.B.Phillips, H.Yu, M.Adler, M.Whitlow, E.Ho, D.Lentz, M.A.Polokoff, B.Subramanyam, J.M.Wu, D.Zhu, R.I.Feldman, D.O.Arnaiz.
 
  ABSTRACT  
 
HTS screening identified 1 with micromolar inhibitory activity against PDK1. Optimization of 1 afforded 4i (BX-517) which has single-digit nanomolar activity against PDK1 and excellent selectivity against PKA.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21459573 D.A.Erlanson, J.W.Arndt, M.T.Cancilla, K.Cao, R.A.Elling, N.English, J.Friedman, S.K.Hansen, C.Hession, I.Joseph, G.Kumaravel, W.C.Lee, K.E.Lind, R.S.McDowell, K.Miatkowski, C.Nguyen, T.B.Nguyen, S.Park, N.Pathan, D.M.Penny, M.J.Romanowski, D.Scott, L.Silvian, R.L.Simmons, B.T.Tangonan, W.Yang, and L.Sun (2011).
Discovery of a potent and highly selective PDK1 inhibitor via fragment-based drug discovery.
  Bioorg Med Chem Lett, 21, 3078-3083.
PDB codes: 3pwy 3qc4
18780147 K.Kaur, and T.T.Talele (2009).
Structure-based CoMFA and CoMSIA study of indolinone inhibitors of PDK1.
  J Comput Aided Mol Des, 23, 25-36.  
18794885 C.Garcia-Echeverria, and W.R.Sellers (2008).
Drug discovery approaches targeting the PI3K/Akt pathway in cancer.
  Oncogene, 27, 5511-5526.  
18972468 C.Peifer, and D.R.Alessi (2008).
Small-molecule inhibitors of PDK1.
  ChemMedChem, 3, 1810-1838.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

spacer
spacer