Several bisphosphonates were examined as inhibitors of yeast GPD (glyceraldehyde-3-phosphate dehydrogenase, EC 188.8.131.52) and PGK (phosphoglycerate kinase, EC 184.108.40.206). The phosphonomethyl analog of 2-deoxy-1,3-bisphosphoglycerate (i.e., 2-oxo-1,5-bisphosphonopentane, 2-oxo-PC5P) is a good inhibitor of PGK (Ki = 0.2 ± 0.08 mM at pH 8.5, 27°C) and a poor inhibitor of GPD (Ki = 20 ± 1 mM, pH 8.5). The shorter, butane, analog (2-oxo-PC4P) binds more tightly to PGK (Ki = 84 ± 6 μM), and about equally well to GPD, as does 2-oxo-PC5P. The 2-oxo-bisphosphonates bind to PGK more tightly (by approx. 4 kJ/mol) than do the corresponding non-carbonyl analogues (1,4-bisphosphonobutane and 1,5-bisphosphonopentane).
|Number of pages||5|
|Journal||Biochimica et Biophysica Acta (BBA)/Protein Structure and Molecular|
|State||Published - 24 Jun 1993|
- Glyceraldehyde-3-phosphate dehydrogenase
- Phosphoglycerate kinase