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PDBsum entry 2uvm

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protein ligands metals links
Transferase PDB id
2uvm
Jmol
Contents
Protein chain
116 a.a. *
Ligands
GVF
Metals
_NA
Waters ×53
* Residue conservation analysis
PDB id:
2uvm
Name: Transferase
Title: Structure of pkbalpha ph domain in complex with a novel inositol headgroup surrogate, benzene 1,2,3,4- tetrakisphosphate
Structure: Rac-alpha serine/threonine-protein kinase. Chain: a. Fragment: pleckstrin homology (ph) domain, residues 1-123. Synonym: protein kinase b alpha, rac-pk-alpha, protein kinase b, pkb, c-akt. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 511693.
Resolution:
1.94Å     R-factor:   0.252     R-free:   0.269
Authors: D.Komander,S.J.Mills,M.N.Trusselle,S.T.Safrany, D.M.F.Van Aalten,B.V.L.Potter
Key ref: S.J.Mills et al. (2007). Novel inositol phospholipid headgroup surrogate crystallized in the pleckstrin homology domain of protein kinase Balpha. ACS Chem Biol, 2, 242-246. PubMed id: 17432822 DOI: 10.1021/cb700019r
Date:
12-Mar-07     Release date:   17-Apr-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P31749  (AKT1_HUMAN) -  RAC-alpha serine/threonine-protein kinase
Seq:
Struc:
480 a.a.
116 a.a.
Key:    PfamA domain  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: ATP + a protein = ADP + a phosphoprotein
ATP
+ protein
= ADP
+ phosphoprotein
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1021/cb700019r ACS Chem Biol 2:242-246 (2007)
PubMed id: 17432822  
 
 
Novel inositol phospholipid headgroup surrogate crystallized in the pleckstrin homology domain of protein kinase Balpha.
S.J.Mills, D.Komander, M.N.Trusselle, S.T.Safrany, D.M.van Aalten, B.V.Potter.
 
  ABSTRACT  
 
Protein kinase B (PKB/Akt) plays a key role in cell signaling. The PH domain of PKB binds phosphatidylinositol 3,4,5-trisphosphate translocating PKB to the plasma membrane for activation by 3-phosphoinositide-dependent protein kinase 1. The crystal structure of the headgroup inositol 1,3,4,5-tetrakisphosphate Ins(1,3,4,5)P4-PKB complex facilitates in silico ligand design. The novel achiral analogue benzene 1,2,3,4-tetrakisphosphate (Bz(1,2,3,4)P4) possesses phosphate regiochemistry different from that of Ins(1,3,4,5)P4 and surprisingly binds with similar affinity as the natural headgroup. Bz(1,2,3,4)P4 co-crystallizes with the PKBalpha PH domain in a fashion also predictable in silico. The 2-phosphate of Bz(1,2,3,4)P4 does not interact with any residue, and the D5-phosphate of Ins(1,3,4,5)P4 is not mimicked by Bz(1,2,3,4)P4. Bz(1,2,3,4)P4 is an example of a simple inositol phosphate surrogate crystallized in a protein, and this approach could be applied to design modulators of inositol polyphosphate binding proteins.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20714465 M.D.Best, H.Zhang, and G.D.Prestwich (2010).
Inositol polyphosphates, diphosphoinositol polyphosphates and phosphatidylinositol polyphosphate lipids: structure, synthesis, and development of probes for studying biological activity.
  Nat Prod Rep, 27, 1403-1430.  
20051961 M.Falasca, D.Chiozzotto, H.Y.Godage, M.Mazzoletti, A.M.Riley, S.Previdi, B.V.Potter, M.Broggini, and T.Maffucci (2010).
A novel inhibitor of the PI3K/Akt pathway based on the structure of inositol 1,3,4,5,6-pentakisphosphate.
  Br J Cancer, 102, 104-114.  
19734051 L.Du-Cuny, Z.Song, S.Moses, G.Powis, E.A.Mash, E.J.Meuillet, and S.Zhang (2009).
Computational modeling of novel inhibitors targeting the Akt pleckstrin homology domain.
  Bioorg Med Chem, 17, 6983-6992.  
18574825 S.J.Mills, F.Vandeput, M.N.Trusselle, S.T.Safrany, C.Erneux, and B.V.Potter (2008).
Benzene polyphosphates as tools for cell signalling: inhibition of inositol 1,4,5-trisphosphate 5-phosphatase and interaction with the PH domain of protein kinase Balpha.
  Chembiochem, 9, 1757-1766.  
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