title: A novel dual allosteric activation mechanism of Escherichia coli ADP-glucose pyrophosphorylase: the role of pyruvate.
abstract: Fructose-1,6-bisphosphate activates ADP-glucose pyrophosphorylase and the synthesis of glycogen in Escherichia coli. Here, we show that although pyruvate is a weak activator by itself, it synergically enhances the fructose-1,6-bisphosphate activation. They increase the enzyme affinity for each other, and the combination increases Vmax, substrate apparent affinity, and decreases AMP inhibition. Our results indicate that there are two distinct interacting allosteric sites for activation. Hence, pyruvate modulates E. coli glycogen metabolism by orchestrating a functional network of allosteric regulators. We postulate that this novel dual activator mechanism increases the evolvability of ADP-glucose pyrophosphorylase and its related metabolic control.
authors.affiliation: Department of Chemistry, Loyola University Chicago, Chicago, Illinois, United States of America; Laboratorio de Enzimología Molecular, Instituto de Agrobiotecnología del Litoral (UNL-CONICET), FBCB Ciudad Universitaria, Santa Fe, Argentina.
authors.forename: Matías D
authors.initials: MD
authors.lastname: Asención Diez
authors.affiliation: Laboratorio de Enzimología Molecular, Instituto de Agrobiotecnología del Litoral (UNL-CONICET), FBCB Ciudad Universitaria, Santa Fe, Argentina.
authors.forename: Mabel C
authors.initials: MC
authors.lastname: Aleanzi
authors.affiliation: Laboratorio de Enzimología Molecular, Instituto de Agrobiotecnología del Litoral (UNL-CONICET), FBCB Ciudad Universitaria, Santa Fe, Argentina.
authors.forename: Alberto A
authors.initials: AA
authors.lastname: Iglesias
authors.affiliation: Department of Chemistry, Loyola University Chicago, Chicago, Illinois, United States of America.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Ballicora
mesh_terms: D000495:Allosteric Site; D004789:Enzyme Activation; D004926:Escherichia coli / Q000201:enzymology*; D005635:Fructosediphosphates / Q000737:chemistry / Q000378:metabolism; D051599:Glucose-1-Phosphate Adenylyltransferase / Q000378:metabolism*; D006003:Glycogen / Q000096:biosynthesis; D007700:Kinetics; D011773:Pyruvates / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D005635:Fructosediphosphates; D011773:Pyruvates; D006003:Glycogen; D051599:Glucose-1-Phosphate Adenylyltransferase; C029063:fructose-1,6-diphosphate
references.citation: Microbiol Mol Biol Rev. 2003 Jun;67(2):213-25, table of contents
references.pmid: 12794190
references.citation: J Biol Chem. 1978 Sep 10;253(17):6197-202
references.pmid: 355250
references.citation: Biochemistry. 2002 Jul 30;41(30):9431-7
references.pmid: 12135365
references.citation: Biochem Biophys Res Commun. 1998 Mar 17;244(2):573-7
references.pmid: 9514953
references.citation: Biochemistry. 2001 Aug 28;40(34):10169-78
references.pmid: 11513594
references.citation: Biochemistry. 2008 Apr 15;47(15):4439-51
references.pmid: 18355040
references.citation: Biochem Biophys Res Commun. 1965 Jan 18;18:180-5
references.pmid: 14282015
references.citation: J Biol Chem. 1969 May 25;244(10):2539-48
references.pmid: 5769989
references.citation: Arch Biochem Biophys. 1970 Sep;140(1):60-74
references.pmid: 5460185
references.citation: Arch Biochem Biophys. 2001 May 15;389(2):159-65
references.pmid: 11339804
references.citation: J Bacteriol. 2012 Nov;194(22):6056-65
references.pmid: 22961847
references.citation: Adv Microb Physiol. 1989;30:183-238
references.pmid: 2700539
references.citation: Photosynth Res. 2004;79(1):1-24
references.pmid: 16228397
references.citation: Nature. 1970 Aug 15;227(5259):680-5
references.pmid: 5432063
references.citation: Metab Eng. 2001 Apr;3(2):115-23
references.pmid: 11289788
references.citation: Arch Biochem Biophys. 1998 Oct 1;358(1):182-8
references.pmid: 9750179
references.citation: Int J Mol Sci. 2013 May 06;14(5):9703-21
references.pmid: 23648478
references.citation: J Biol Chem. 2006 Dec 29;281(52):40473-84
references.pmid: 17079236
references.citation: BMC Evol Biol. 2013 Feb 21;13:51
references.pmid: 23433303
references.citation: EMBO J. 2005 Feb 23;24(4):694-704
references.pmid: 15692569
references.citation: Biochimie. 2011 Oct;93(10):1816-23
references.pmid: 21741429
references.citation: Biotechnol Annu Rev. 1996;2:259-79
references.pmid: 9704099
references.citation: Nucleic Acids Res. 2003 Jul 1;31(13):3784-8
references.pmid: 12824418
references.citation: J Bacteriol. 2007 Jul;189(14):5325-33
references.pmid: 17496097
references.citation: J Biol Chem. 2001 Dec 7;276(49):46319-25
references.pmid: 11567027
references.citation: J Bacteriol. 2012 Mar;194(6):1485-93
references.pmid: 22210767
references.citation: J Biol Chem. 1978 Nov 10;253(21):7638-45
references.pmid: 359552
references.citation: PLoS One. 2013 Jun 24;8(6):e66824
references.pmid: 23826149
references.citation: Biochemistry. 1996 Mar 5;35(9):3115-21
references.pmid: 8608152
references.citation: Biochemistry. 1966 Jun;5(6):1833-45
references.pmid: 4290042
references.citation: Arch Biochem Biophys. 1998 Sep 1;357(1):13-21
references.pmid: 9721178
references.citation: Mol Microbiol. 2013 Dec;90(5):1011-27
references.pmid: 24112771
references.citation: FEBS Lett. 2004 Aug 27;573(1-3):99-104
references.pmid: 15327982
references.citation: Anal Biochem. 2006 May 1;352(1):145-7
references.pmid: 16574055
references.citation: Arch Biochem Biophys. 1990 Jul;280(1):175-80
references.pmid: 2162151