Identification of a Mitochondrial-Binding Site on the XXXX -Terminal End of Hexokinase II.

@entity1522 @entity1472 @entity5 @entity3793 @entity4613 @entity1521 @entity3689 @entity413
UNASSIGNED: Hexokinase II is responsible for the first step in the glycolysis pathway by adding a @entity4613 onto the @entity413 molecule so it can proceed down the pathway to produce the energy for continuous @entity5 cell growth. @entity5 cells overexpress the hexokinase II enzyme. In fact, it is the overexpression of the hexokinase II enzyme that makes the diagnosis of @entity5 possible when imaged by positron emission tomography (PET). Hexokinase II binds to the voltage-dependent anion channel (VDAC) located on the mitochondrial outer membrane (MOM). When bound to the MOM, hexokinase II is blocking a major cell death pathway. Thus, hexokinase II is responsible for two characteristics of @entity5 cells, rapid @entity5 growth and @entity5 cells to undergo apoptosis. One method to identify novel compounds that may interfere with the hexokinase II-VDAC binding site is to create a molecular model using the crystal structure of hexokinase II. However, the @entity3689 (s) responsible for hexokinase II binding to VDAC are not known. Therefore, a series of truncations and point mutations were made to the @entity1472 -terminal end of hexokinase II to identify the binding site to VDAC. Deletions of the first 10 and 20 @entity1522 indicated that important @entity3689 (s) for binding were located within the first 10 @entity1522 . Next, a series of point mutations were made within the first 10 @entity1522 . It is clear from the immunofluorescence images and immunoblot results that mutating the fifth @entity3689 from @entity3793 to @entity1521 completely abolished binding to the MOM.
