PDBsum entry 2x6i

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Transferase PDB id
Protein chains
546 a.a. *
090 ×2
* Residue conservation analysis
PDB id:
Name: Transferase
Title: The crystal structure of the drosophila class iii pi3-kinase vps34 in complex with pik-90
Structure: Phosphotidylinositol 3 kinase 59f. Chain: a, b. Fragment: helical domain, kinase domain residues 258-949. Synonym: gh13170p, vps34. Ec:,, Engineered: yes. Mutation: yes
Source: Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Expressed in: escherichia coli. Expression_system_taxid: 562.
3.40Å     R-factor:   0.220     R-free:   0.279
Authors: S.Miller,B.Tavshanjian,A.Oleksy,O.Perisic,B.T.Houseman,K.M.S R.L.Williams
Key ref: S.Miller et al. (2010). Shaping development of autophagy inhibitors with the structure of the lipid kinase Vps34. Science, 327, 1638-1642. PubMed id: 20339072
17-Feb-10     Release date:   07-Apr-10    
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Protein chains
Pfam   ArchSchema ?
Q9W1M7  (Q9W1M7_DROME) -  GH13170p
949 a.a.
546 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Phosphatidylinositol 3-kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

1-Phosphatidyl-myo-inositol Metabolism
      Reaction: ATP + 1-phosphatidyl-1D-myo-inositol = ADP + 1-phosphatidyl-1D-myo- inositol 3-phosphate
+ 1-phosphatidyl-1D-myo-inositol
+ 1-phosphatidyl-1D-myo- inositol 3-phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     phosphatidylinositol-mediated signaling   2 terms 
  Biochemical function     transferase activity, transferring phosphorus-containing groups     3 terms  


Science 327:1638-1642 (2010)
PubMed id: 20339072  
Shaping development of autophagy inhibitors with the structure of the lipid kinase Vps34.
S.Miller, B.Tavshanjian, A.Oleksy, O.Perisic, B.T.Houseman, K.M.Shokat, R.L.Williams.
Phosphoinositide 3-kinases (PI3Ks) are lipid kinases with diverse roles in health and disease. The primordial PI3K, Vps34, is present in all eukaryotes and has essential roles in autophagy, membrane trafficking, and cell signaling. We solved the crystal structure of Vps34 at 2.9 angstrom resolution, which revealed a constricted adenine-binding pocket, suggesting the reason that specific inhibitors of this class of PI3K have proven elusive. Both the phosphoinositide-binding loop and the carboxyl-terminal helix of Vps34 mediate catalysis on membranes and suppress futile adenosine triphosphatase cycles. Vps34 appears to alternate between a closed cytosolic form and an open form on the membrane. Structures of Vps34 complexes with a series of inhibitors reveal the reason that an autophagy inhibitor preferentially inhibits Vps34 and underpin the development of new potent and specific Vps34 inhibitors.

Literature references that cite this PDB file's key reference

  PubMed id Reference
22358332 B.Vanhaesebroeck, L.Stephens, and P.Hawkins (2012).
PI3K signalling: the path to discovery and understanding.
  Nat Rev Mol Cell Biol, 13, 195-203.  
21164513 A.Fleming, T.Noda, T.Yoshimori, and D.C.Rubinsztein (2011).
Chemical modulators of autophagy as biological probes and potential therapeutics.
  Nat Chem Biol, 7, 9.  
21385607 K.V.Powis, and L.K.MacDougall (2011).
The localisation of PtdIns3P in Drosophila fat responds to nutrients but not insulin: a role for Class III but not Class II phosphoinositide 3-kinases.
  Cell Signal, 23, 1153-1161.  
20885446 M.Pozuelo-Rubio (2011).
Regulation of autophagic activity by 14-3-3ζ proteins associated with class III phosphatidylinositol-3-kinase.
  Cell Death Differ, 18, 479-492.  
21362552 X.Zhang, O.Vadas, O.Perisic, K.E.Anderson, J.Clark, P.T.Hawkins, L.R.Stephens, and R.L.Williams (2011).
Structure of lipid kinase p110β/p85β elucidates an unusual SH2-domain-mediated inhibitory mechanism.
  Mol Cell, 41, 567-578.
PDB code: 2y3a
20571384 A.Huett, G.Goel, and R.J.Xavier (2010).
A systems biology viewpoint on autophagy in health and disease.
  Curr Opin Gastroenterol, 26, 302-309.  
20740284 C.Burman, and N.T.Ktistakis (2010).
Autophagosome formation in mammalian cells.
  Semin Immunopathol, 32, 397-413.  
20977678 H.Stenmark (2010).
The Sir Hans Krebs Lecture. How a lipid mediates tumour suppression. Delivered on 29 June 2010 at the 35th FEBS Congress in Gothenburg, Sweden.
  FEBS J, 277, 4837-4848.  
20730586 J.A.Rodriguez-Navarro, and A.M.Cuervo (2010).
Autophagy and lipids: tightening the knot.
  Semin Immunopathol, 32, 343-353.  
20609406 P.Workman, and I.Collins (2010).
Probing the Probes: Fitness Factors For Small Molecule Tools.
  Chem Biol, 17, 561-577.  
20811353 Z.Yang, and D.J.Klionsky (2010).
Eaten alive: a history of macroautophagy.
  Nat Cell Biol, 12, 814-822.  
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 code is shown on the right.