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The structure of mammalian hexokinase-1

Nature Structural Biology volume 5, pages 555–560 (1998)Cite this article

Abstract

We have determined the structures of the glucose-6-phosphate (G6P)-inhibitable 100,000 M r Type I hexokinase from rat and the G6P-sensitive 50,000 M r hexokinase from Schistosoma mansoni at a resolution of 2.8 and 2.6 Å respectively. The structures define the glucose and G6P binding sites in these enzymes, suggest the mechanisms of intradomain G6P inhibition and activity loss in the Type I hexokinase N-terminal half, and reveal the structure of the membrane targeting motif that integrates the Type I hexokinase into the outer mitochondrial membrane.

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Figure 1: Ribbon drawings of the rHK-I a, dimer and b, monomer. In (b),the strictly helical portion of the linker between the rHK-In and rHK-Ic domains is colored blue with a putative pivot point indicated by an asterisk.
Figure 2: Views of the crystal contacts along the a-axis in the Type 2 crystals.
Figure 3: a, Superpositions of rHK-In (blue) and rHK-Ic (green) domains with SHEX (orange).

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Acknowledgements

We acknowledge the financial support of the Michigan State University Foundation (R.M.G.), the REF Center for Protein Structure, Function, and Design (R.M.G.) and a PHS-NIH grant (J.E.W.).

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Authors and Affiliations

  1. Department of Biochemistry, Michigan State University, East Lansing, Michigan, USA

    Anne M. Mulichak, John E. Wilson, Kaillathe Padmanabhan & R. Michael Garavito

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  1. Anne M. Mulichak
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  4. R. Michael Garavito
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Correspondence to Anne M. Mulichak or R. Michael Garavito.

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Mulichak, A., Wilson, J., Padmanabhan, K. et al. The structure of mammalian hexokinase-1. Nat Struct Mol Biol 5, 555–560 (1998). https://doi.org/10.1038/811

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