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Mechanism of ATP‐dependent release of wild type and mutant human brain hexokinases from mitochondria
Author(s) -
Mehyar Nimer,
Watanabe Muneaki,
Shen Lu,
Skaff Andrew,
Honzatko Richard B
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.510.6
Subject(s) - voltage dependent anion channel , hexokinase , adenosine triphosphate , mitochondrion , biochemistry , adenosine diphosphate , inner membrane , nucleotide , mutant , inner mitochondrial membrane , binding site , biology , bacterial outer membrane , enzyme , chemistry , glycolysis , gene , escherichia coli , platelet , platelet aggregation , immunology
Adenosine 5′‐triphosphate (ATP) can release hexokinase I (HKI) from its binding site on outer mitochondrial membrane. The mechanism of ATP release of HKI from mitochondria, however, is not clear: ATP binds to the C‐terminal half of HKI as a substrate and to the N‐terminal half near the membrane binding element. ATP also binds to voltage dependent anion channel (VDAC), the integral membrane component that binds HKI to the mitochondrion. Fluorescent nucleotide analogue 2′,3′‐ O ‐(2,4,6‐trinitrophenyl) adenosine 5′‐diphosphate (TNP‐ADP) binds with high affinity to the active site of HKI and to VDAC, but not to the N‐terminal half of HKI. ATP and TNP‐ADP separately release wild type HKI and the truncated N‐domain of HKI from mitochondria, excluding nucleotide binding to either the N‐ or C‐half of HKI in the release mechanism. Results here are consistent with a HKI release mechanism in which ATP or TNP‐ADP bind to VDAC. This research is supported by NIH grant NS 10546.