Eliminylation: a post-translational modification catalyzed by phosphothreonine lyases.
We propose the classification of a protein post-translational modification, eliminylation, based on the recently delineated mechanism of the Shigella OspF and Salmonella SpvC phosphothreonine lyases. These bacterial type-III secretion-system virulence factors are injected into eukaryotic cells and inhibit signalling by irreversibly inactivating mitogen-activated protein kinases (MAPKs). Remarkably, they employ an unusual beta-elimination reaction, removing the phosphate from phosphothreonine and converting it into dehydrobutyrine (an alkene). Eliminylated cysteine can also be produced by decarboxylation and eliminylated serine and threonine by dehydration; these residues are found in the eye lens and in bacterial lantibiotics. We postulate that eliminylation might be a widespread regulatory modification, and we propose the use of phosphothreonine lyases as in vivo MAPK inhibitors both therapeutically and to investigate MAPK signalling regulation.
Brennan
Damian F
DF
Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK. damian.brennan@icr.ac.uk
Barford
David
D
D008190:Lyases / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D010769:Phosphothreonine / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction / Q000502:physiology
D010769:Phosphothreonine; D020928:Mitogen-Activated Protein Kinases; D008190:Lyases