Pr. Kuser et al., The high resolution crystal structure of yeast hexokinase PII with the correct primary sequence provides new insights into its mechanism of action, J BIOL CHEM, 275(27), 2000, pp. 20814-20821
Hexokinase is the first enzyme in the glycolytic pathway, catalyzing the tr
ansfer of a phosphoryl group from ATP to glucose to form glucose 6-phosphat
e and ADP. Two yeast hexokinase isozymes are known, namely PI and PII. The
crystal structure of yeast hexokinase PII from Saccharomyces cerevisiae wit
hout substrate or competitive inhibitor is determined and refined in a tetr
agonal crystal form at 2.2-Angstrom resolution The folding of the peptide c
hain is very similar to that of Schistosoma mansoni and previous yeast hexo
kinase models despite only 30% sequence identity between them. Distinct dif
ferences in conformation are found that account for the absence of glucose
in the binding site. Comparison of the current model with S. mansoni and ye
ast hexokinase PI structures both complexed with glucose shows in atomic de
tail the rigid body domain closure and specific loop movements as glucose b
inds. A hydrophobic channel formed by strictly conserved hydrophobic residu
es in the small domain of the hexokinase is identified. The channel's mouth
is close to the active site and passes through the small domain to its sur
face. The possible role of the observed channel in proton transfer is discu
ssed.