Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P20020 (
adenosine triphosphatase
)
3,299
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Shaping development of autophagy inhibitors with the structure of the lipid kinase Vps34. 2047 24
