Active-centre torsion-angle strain revealed in 1.6 A-resolution structure of histidine-containing phosphocarrier protein.
The histidine-containing phosphocarrier protein (HPr) is a central component of the phosphoenolpyruvate: sugar phosphotransferase system that transports carbohydrates across the cell membrane of bacteria. A typical phosphotransfer sequence is phosphoenolpyruvate-->enzyme I-->HPr-->enzyme II/IIIsugar-->sugar. This is thermodynamically favourable owing to the participation of the high-energy phosphoenolpyruvate. We report here the structure of HPr from Streptococcus faecalis determined at 1.6 A resolution. Remarkable disallowed Ramachandran torsion angles at the active centre, revealed by the X-ray structure, demonstrate a unique example of torsion-angle strain that is probably directly involved in protein function. During phosphorylation, the active-centre torsion-angle strain should facilitate the phosphotransfer reaction by lowering the activation-energy barrier. A recently reported Bacillus subtilis HPr structure, which represents the phosphorylated state of HPr with no torsion-angle strain, provides direct evidence supporting our hypothesis that torsion-angle strain plays a direct part in the function of HPr. An HPr phosphotransfer cycling mechanism is proposed, based primarily on the structures of HPr and other phosphotransferase system proteins.
Jia
Z
Z
Department of Chemistry, University of Saskatchewan, Saskatoon, Canada.
Vandonselaar
M
M
Quail
J W
JW
Delbaere
L T
LT
D001426:Bacterial Proteins / Q000737:chemistry*; D013293:Enterococcus faecalis / Q000737:chemistry; D006639:Histidine; D006860:Hydrogen Bonding; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System / Q000737:chemistry*; D011487:Protein Conformation; D014961:X-Ray Diffraction
D001426:Bacterial Proteins; D006639:Histidine; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System; C030182:phosphocarrier protein HPr