PMID- 8567628
OWN - NLM
STAT- MEDLINE
DCOM- 19960301
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 271
IP  - 4
DP  - 1996 Jan 26
TI  - Functional organization of mammalian hexokinase II. Retention of catalytic and 
      regulatory functions in both the NH2- and COOH-terminal halves.
PG  - 1849-52
AB  - The mammalian hexokinase (HK) family includes three closely related 100-kDa 
      isoforms (HKI-III) that are thought to have arisen from a common 50-kDa precursor 
      by gene duplication and tandem ligation. Previous studies of HKI indicated that a 
      glucose 6-phosphate (Glu-6-P)-regulated catalytic site resides in the 
      COOH-terminal half of the molecule and that the NH2-terminal half contains only a 
      Glu-6-P binding site. In contrast, we now show that proteins representing both 
      halves of human and rat HKII have catalytic activity and that each is inhibited 
      by Glu-6-P. The intact enzyme and the NH2- and COOH-terminal halves of the enzyme 
      each increase glucose utilization when expressed in Xenopus oocytes. Mutations 
      corresponding to either Asp-209 or Asp-657 in the intact enzyme completely 
      inactivate the NH2- and COOH-terminal half enzymes, respectively. Mutation of 
      either of these sites results in a 50% reduction of activity in the 100-kDa 
      enzyme. Mutation of both sites results in a complete loss of activity. This 
      suggests that each half of the HKII molecule retains catalytic activity within 
      the 100-kDa protein. These observations indicate that HKI and HKII are 
      functionally distinct and have evolved differently.
FAU - Ardehali, H
AU  - Ardehali H
AD  - Department of Molecular Physiology and Biophysics, Vanderbilt University School 
      of Medicine, Nashville, Tennessee 37232, USA.
FAU - Yano, Y
AU  - Yano Y
FAU - Printz, R L
AU  - Printz RL
FAU - Koch, S
AU  - Koch S
FAU - Whitesell, R R
AU  - Whitesell RR
FAU - May, J M
AU  - May JM
FAU - Granner, D K
AU  - Granner DK
LA  - eng
GR  - DK19925/DK/NIDDK NIH HHS/United States
GR  - DK20593/DK/NIDDK NIH HHS/United States
GR  - DK46867/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA Primers)
RN  - 0 (Glucosephosphates)
RN  - 0 (Recombinant Proteins)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Biological Evolution
MH  - DNA Primers/chemistry
MH  - Glucose/metabolism
MH  - Glucosephosphates/metabolism
MH  - Hexokinase/*chemistry
MH  - Humans
MH  - Kinetics
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Rats
MH  - Recombinant Proteins
MH  - Structure-Activity Relationship
MH  - Xenopus laevis
EDAT- 1996/01/26 00:00
MHDA- 1996/01/26 00:01
CRDT- 1996/01/26 00:00
PHST- 1996/01/26 00:00 [pubmed]
PHST- 1996/01/26 00:01 [medline]
PHST- 1996/01/26 00:00 [entrez]
AID - S0021-9258(17)46109-6 [pii]
AID - 10.1074/jbc.271.4.1849 [doi]
PST - ppublish
SO  - J Biol Chem. 1996 Jan 26;271(4):1849-52. doi: 10.1074/jbc.271.4.1849.