Abstract
The active centers of phosphoglucose isomerase (PGI) and the hexose phosphate isomerase domain (HPI) of glucosamine-6-P (GlcN-6-P) synthase demonstrate apparent similarity in spatial arrangement of critical amino acid residues, except Arg272 of the former and Lys603 and Lys485 of the latter. Ten derivatives of d-hexitol-6-P, 5-phosphoarabinoate, or 6-phosphogluconate, structural analogues of putative cis-enolamine or cis-enolate intermediates, were tested as inhibitors of fungal GlcN-6-P synthase and PGI. None of the investigated compounds demonstrated equally high inhibitory potential against both enzymes. 2-Amino-2-deoxy-D-mannitol 6-P was found to be the strongest GlcN-6-P synthase inhibitor in the series, with an inhibition constant equal to 9.0 (+/-1.0) x 10(-6)M. On the contrary, 5-phosphoarabinoate (5PA) exhibited specificity for PGI, with K(i)=2.2 (+/-0.1) x 10(-6) M. N-acetylation substantially lowered the GlcN-6-P synthase inhibitory potential of 2-amino-2-deoxy-D-glucitol-6-P but strongly enhanced inhibitory potential of this compound towards PGI. Molecular modeling studies revealed that interactions of the C1-C2 part of transition state analogue inhibitors with the respective areas demonstrating different distributi...Continue Reading
References
May 1, 1976·Journal of General Microbiology·M KenigE P Abraham
Dec 1, 1975·Journal of Bacteriology·W L Whelan, C E Ballou
Jul 1, 1991·Archives of Biochemistry and Biophysics·M A DenisotB Badet
Oct 1, 1991·European Journal of Biochemistry·B Golinelli-Pimpaneau, B Badet
Feb 1, 1971·Journal of Bacteriology·M Sarvas
Jun 26, 1981·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·I A Rose
Sep 18, 1998·Structure·A TeplyakovI Polikarpov
Jan 5, 1999·Bioorganic & Medicinal Chemistry Letters·R HardréA Gaudemer
Feb 6, 1999·The Journal of Biological Chemistry·S MilewskiG W Gooday
Mar 26, 1999·Protein Science : a Publication of the Protein Society·A TeplyakovB Badet
Nov 30, 1999·Carbohydrate Research·R Hardré, L Salmon
Jan 5, 2000·The Journal of Biological Chemistry·S L Bearne, C Blouin
Feb 2, 2000·Biochemistry·C J JefferyG A Petsko
Aug 5, 2000·Il Farmaco·E Borowski
Oct 13, 2000·Journal of Enzyme Inhibition·R HardréF R Opperdoes
May 1, 2001·Biochemistry·C J JefferyL Salmon
Jun 27, 2001·Biochemistry·J H LeeC J Jeffery
Nov 9, 2001·Journal of Molecular Biology·A TeplyakovM A Badet-Denisot
May 2, 2002·Proceedings of the National Academy of Sciences of the United States of America·Diana ArsenievaConstance J Jeffery
Jun 5, 2002·Biochimica Et Biophysica Acta·Sławomir Milewski
Jun 11, 2002·Medical Mycology·A M Janiak, S Milewski
Mar 28, 2003·Bioorganic & Medicinal Chemistry·Agnieszka M JaniakSławomir Milewski
Citations
Jan 31, 2012·Bioprocess and Biosystems Engineering·Ning ChenCleo Kontoravdi
Aug 8, 2007·Journal of Molecular Biology·Joanna RaczynskaWojciech Rypniewski
Jun 20, 2017·Carbohydrate Research·Kornelia SkarbekMaria J Milewska
Dec 7, 2007·The Journal of Biological Chemistry·Patricia L TaylorMurray S Junop
Feb 18, 2020·Current Pharmaceutical Design·Amit LatherAnurag Khatkar
May 13, 2008·Journal of the American Chemical Society·Ruibo WuYirong Mo
Sep 22, 2018·ACS Chemical Biology·Yi-Fan XuJoshua D Rabinowitz
Sep 21, 2007·Analytical Biochemistry·Yanyan LiMarie-Ange Badet-Denisot
Oct 9, 2007·Bioorganic & Medicinal Chemistry Letters·Anna MelcerSławomir Milewski
Feb 19, 2008·Archives of Biochemistry and Biophysics·Philippe DurandMarie-Ange Badet-Denisot