An atomic model for protein-protein phosphoryl group transfer.
The high resolution crystal structures of two interacting proteins from the phosphoenolpyruvate:sugar phosphotransferase system, the histidine-containing phosphocarrier protein (HPr) and the IIA domain of glucose permease (IIA(Glc)) from Bacillus subtilis, provide the basis for modeling the transient binary complex formed during the phosphoryl group transfer. The complementarity of the interacting surfaces implies that no major conformational transition is required. The negatively charged phosphoryl group is buried in the interface, suggesting a key role for electrostatic interactions. It is proposed that the phosphoryl transfer is triggered by a switch between two salt bridges involving Arg-17 of the HPr. The first, prior to phosphoryl group transfer, is intramolecular, with the phosphorylated His-15. The second, during the transfer, is intermolecular, with 2 aspartate residues associated with the active site of IIA(Glc). Such alternating ion pairs may be mechanistically important in other protein-protein phosphotransfer reactions.
Herzberg
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Center for Advanced Research in Biotechnology, Maryland Biotechnology Institute, University of Maryland, Rockville 20850.
D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000201:enzymology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D004563:Electrochemistry; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System / Q000737:chemistry* / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism; D010766:Phosphorylation; D011487:Protein Conformation
D001426:Bacterial Proteins; D010750:Phosphoproteins; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System; C030182:phosphocarrier protein HPr; C031629:phosphoenolpyruvate-glucose phosphotransferase