Plasmodium vivax cGMP-dependent protein kinase (PVX_084705)

Target ID:

PVX_084705

Deposition Date:

Friday 27th September 2013

Families:

Protein Kinase

Related Diseases:

Parasitic disease

Structure type:

apo

Download Coordinates:

Superceded by 5DYL

Authors:

Wernimont AK, Tempel W, He H, Seitova A, Hills T, Neculai AM, Baker DA, Flueck C, Kettleborough CA, Arrowsmith CH, Edwards AM, Bountra C, Hui R, Hutchinson A, Ell Bakkouri M

Site:

Toronto

4MYI

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Structure Details

The two protein kinases central in cyclic nucleotide signaling are PKA and PKG. Structural biology has been a key tool in mechanistic understanding of how PKA is activated by cAMP, particularly in elucidating the dynamic interactions between the regulatory and catalytic subunits in a tetrameric holoenzyme. PKG features a different combinatorial assembly of cyclic nucleotide binding domains (CNBs) and a kinase domain distinct from PKA, fusing them in a single protein. How PKG behaves differently from PKA as a result of this fusion is a longstanding puzzle in the study of protein kinases and second messenger signaling. We present herein the auto-inhibited structure of Plasmodium vivax PKG, a regulator of multiple life cycle stages of the parasite responsible for malaria. This structure of full-length PKG from any organism reveals four CNBs and the KD arranged in a pentagon. The protein crystallized as a swapped-domain dimer. Following up experiments suggest that this is an artifact of crystallization and the protein is in fact monomeric.