Zc. Jia et al., STRUCTURAL COMPARISON OF THE HISTIDINE-CONTAINING PHOSPHOCARRIER PROTEIN HPR, Biochemistry and cell biology, 72(5-6), 1994, pp. 202-217
The phosphocarrier protein HPr is a central component of the bacterial
phosphoenolpyruvate:sugar phosphotransferase system (PTS) that is res
ponsible for carbohydrate uptake in many bacterial species. A number o
f three-dimensional structures of HPrs from both Gram-positive and Gra
m-negative bacteria have been determined; the overall folding topology
of HPr is an open-faced beta-sandwich composed of three alpha-helices
and a beta-sheet. A detailed structural comparison of these HPrs has
been carried out. Besides the overall main chain folding, many detaile
d structural features are well conserved in all HPr structures. The th
ree x-ray structures of HPrs from Escherichia coli, Streptococcus faec
alis, and Bacillus subtilis show considerable overall similarity with
respect to the positions of the C alpha atoms. A significant structura
l difference between HPrs from Gram-positive and Gram-negative bacteri
a is found in the region of Gly54, owing to the steric effects of Tyr3
7 in HPrs from the Gram-positive species. The region around Gly54 is i
nvolved in the binding of HPr to other PTS proteins and the difference
s in this region may be responsible for some of the poor functional co
mplementation between HPrs from Gram-positive and Gramnegative species
. The active center region, residues 12-18, appears to have significan
t differences in the comparisons between the overall structures. These
differences support the proposal that phosphorylation and dephosphory
lation of the active site His15 is accompanied by conformational chang
es. However, a local structural comparison of residues 12-18 from the
x-ray structures of HPrs from E. coli and B. subtilis, and the two-dim
ensional nuclear magnetic resonance structure of B. subtilis HPr sugge
sts that there is a conserved active center involving residues His15,
Arg17, and Pro18, which shows little conformational change during the
phosphorylation cycle. The results of other experimental approaches, i
ncluding site-directed mutagenesis and NMR spectroscopy, are in some c
ases difficult to rationalize with some of the details of the structur
es, but do appear to favour the conclusion that little conformational
change occurs.