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GTP plus water mimic ATP in the active site of protein kinase CK2

Nature Structural Biology volume 6, pages 1100–1103 (1999)Cite this article

Abstract

The structures of the catalytic subunit of protein kinase CK2 from Zea mays complexed with Mg2+ and with analogs of ATP or GTP were determined to 2.2 Å resolution. Unlike most other protein kinases, CK2 from various sources shows 'dual-cosubstrate specificity', that is, the ability to efficiently use either ATP or GTP as a cosubstrate. The structures of these complexes demonstrate that water molecules are critical to switch the active site of CK2 from an ATP- to a GTP-compatible state. An understanding of the structural basis of dual-cosubstrate specificity may help in the design of drugs that target CK2 or other kinases with this property.

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Figure 1: Enzyme kinetics of rmCK2α in Lineweaver-Burk representation.
Figure 2: The binding site of the nucleotide purine base in rmCK2α.
Figure 3: Global view of the rmCK2α structure in complex with AMPPNP and Mg2+.
Figure 4: Stereoview of ATP in complex with the interdomain hinge region of CAPK.

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Authors and Affiliations

  1. Universität zu Köln, Institut für Biochemie, Zülpicher Straβe 47, Köln, D-50674, Germany

    Karsten Niefind, Michael Pütter & Dietmar Schomburg

  2. Odense Universitet, Biokemisk Institut, Odense, Campusvej 55, DK-5230, Denmark

    Barbara Guerra & Olaf-Georg Issinger

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  1. Karsten Niefind
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  2. Michael Pütter
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  3. Barbara Guerra
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  4. Olaf-Georg Issinger
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  5. Dietmar Schomburg
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Correspondence to Karsten Niefind.

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Niefind, K., Pütter, M., Guerra, B. et al. GTP plus water mimic ATP in the active site of protein kinase CK2. Nat Struct Mol Biol 6, 1100–1103 (1999). https://doi.org/10.1038/70033

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