Suicide inhibition of alpha-oxamine synthases: structures of the covalent adducts of 8-amino-7-oxononanoate synthase with trifluoroalanine.
The irreversible inhibition of 8-amino-7-oxononanoate synthase by trifluoroalanine involves decarboxylative defluorination of the inhibitor-PLP aldimine followed by attack of the conjugated imine by the amino group of the active site lysine to afford a covalently bound difluorinated intermediate which can subsequently undergo further HF losses and hydrolysis to afford a 2-(pyridoximine phosphate) acetoyl protein adduct.
School of Biology, Swann Building, University of Edinburgh, Mayfield Road, Edinburgh, UKEH9 3JR.
Dmitriy
D
Alexeev
Robert L
RL
Baxter
Dominic J
DJ
Campopiano
Olivier
O
Kerbarh
Lindsay
L
Sawyer
Nicholas
N
Tomczyk
Rory
R
Watt
Scott P
SP
Webster
D000217:Acyltransferases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D000409:Alanine / Q000031:analogs & derivatives* / Q000378:metabolism*; D001665:Binding Sites; D002384:Catalysis; D006868:Hydrolysis; D008025:Ligases / Q000037:antagonists & inhibitors*; D008239:Lysine / Q000737:chemistry; D008958:Models, Molecular; D011487:Protein Conformation
D000217:Acyltransferases; C021929:8-amino-7-oxononanoate synthase; D008025:Ligases; D008239:Lysine; D000409:Alanine