Phosphonate inhibitors of glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase

Yaw-Kuen Li, Larry D. Byers*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Several bisphosphonates were examined as inhibitors of yeast GPD (glyceraldehyde-3-phosphate dehydrogenase, EC 1.2.1.12) and PGK (phosphoglycerate kinase, EC 2.7.2.3). 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).

Original languageEnglish
Pages (from-to)17-21
Number of pages5
JournalBiochimica et Biophysica Acta (BBA)/Protein Structure and Molecular
Volume1164
Issue number1
DOIs
StatePublished - 24 Jun 1993

Keywords

  • Glyceraldehyde-3-phosphate dehydrogenase
  • Inhibition
  • Phosphoglycerate kinase
  • Phosphonate

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