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(1) TETRAMER PRESERVED IN CRYSTAL STRUCTURES OF MAMMALIAN HEXOKINASE I MAY BE RELATED TO THE OLIGOMERIC STATE OF THE ENZYE IN ASSOCIATION WITH THE MITOCHONDRIAL PERMEABILITY TRANSITION PORE A.E. Aleshin, R.B. Honzatko and
H.J. Fromm
Mammalian hexokinase I (HKI), the first enzyme of glycolysis, is functional as a tetramer when associated with mitochondrial permeability transition pores (PTP) in brain. In solution, however, HKI exists as a monomer or a homodimer depending on the protein concentration. The physiological role of dimeric HKI is unsettled. It is likely to be a component of a higher oligomeric state, the formation of which is promoted by interactions with PTP. The crystal structures of dimeric HKI, complexed with different ligands, suggest dimers are catalytically functional. In three different crystal forms of the enzyme the dimers associate as identical noncrystallographic tetramers, the organization of which is consistent with known properties of oligomeric HKI in its complex with PTP. The crystal structures also reveal an additional ADP/ATP binding site near the N-terminal membrane-binding helix, which may regulate the interaction of HKI with mitochondrial porin (VDAC). The structural organization of the tetramer suggests that only two active sites of HKI interact with PTP, while the other two active sites may function as allosteric regulatory sites. The model requires PTP to have an internal 2-fold symmetry to promote formation of tetrameric HKI.
For further information contact...Carmen Mannella: carmen@wadsworth.org |
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