Journal:Acta Cryst D:S2059798319002912

Crystal structure of the pseudoenzyme PDX1.2 in complex with its cognate enzyme PDX1.3

Graham C. Robinson, Markus Kaufmann, Céline Roux, Jacobo Martinez-Font, Michael Hothorn, Stéphane Thore, and Teresa B. Fitzpatrick ^[1]

Molecular Tour
PDX1 is a component of the protein complex responsible for biosynthesis of vitamin B6 in plants. Plants may carry several copies of PDX1. Arabidopsis has three paralogs, PDX1.1, PDX1.2, PDX1.3. Interestingly, whereas PDX1.1 and PDX1.3 are catalytically active, PDX1.2 is a pseudoenzyme: a paralog that lacks the key catalytic residues and is therefore inactive, but can interact with and modulate the activity of its catalytic partners. Notably, in the plant lineage most eudicota carry a copy of PDX1.2 but monocots do not. Here we aimed to determine the 3D structure of PDX1.2 in complex with its cognate enzyme PDX1.3 by X-ray crystallography, to provide insight into the nature of this interaction. Our data of several PDX1.2/PDX1.3 complex structures indicate that the pseudoenzyme PDX1.2 adopts the same fold as its enzyme partner, PDX1.3; but that these protein complexes exhibit statistical disorder likely due to this similarity. Consequently, the structure of these complexes are composites of both proteins, revealing what may be an intrinsic limitation in the crystallographic investigation of enzyme:pseudoenzyme complexes. Nonetheless, the structures determined reveal enhanced flexibility in key catalytic regions for the initial steps of vitamin B6 biosynthesis and provide insight into the generation of this vitamin, essential for all domains of life.

References

1. ↑ Robinson GC, Kaufmann M, Roux C, Martinez-Font J, Hothorn M, Thore S, Fitzpatrick TB. Crystal structure of the pseudoenzyme PDX1.2 in complex with its cognate enzyme PDX1.3: a total eclipse. Acta Crystallogr D Struct Biol. 2019 Apr 1;75(Pt 4):400-415. doi:, 10.1107/S2059798319002912. Epub 2019 Apr 4. PMID:30988257 doi:http://dx.doi.org/10.1107/S2059798319002912