Structure of the Pseudokinase VRK3 Reveals a Degraded Catalytic Site, a Highly Conserved Kinase Fold, and a Putative Regulatory Binding Site
2009

Structure of the Pseudokinase VRK3

publication Evidence: high

Author Information

Author(s): Eric D. Scheeff, Jeyanthy Eswaran, Gabor Bunkoczi, Stefan Knapp, Gerard Manning

Primary Institution: Salk Institute for Biological Studies

Hypothesis

The study investigates the structural details of the pseudokinase VRK3 and its loss of catalytic activity compared to its active relative VRK2.

Conclusion

The structure of VRK3 reveals significant changes in the active site that prevent ATP binding, while retaining a conserved fold that suggests it may have regulatory functions.

Supporting Evidence

  • VRK3 cannot bind ATP due to residue substitutions in the binding pocket.
  • VRK3 shares structural similarity with VRK2 despite being catalytically inactive.
  • The study provides insights into the evolutionary retention of VRK3 despite its loss of enzymatic function.

Takeaway

VRK3 is a protein that looks like it should work, but it can't because it has some broken parts. It still helps other proteins do their jobs.

Methodology

The study used X-ray crystallography to determine the structures of VRK3 and VRK2, comparing their active sites and overall folds.

Limitations

The study primarily focuses on structural analysis and does not explore the functional implications of VRK3 in vivo.

Digital Object Identifier (DOI)

10.1016/j.str.2008.10.018

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