Mechanism for activation of triosephosphate isomerase by phosphite dianion: the role of a hydrophobic clamp.

Journal of the American Chemical Society
M Merced MalabananJohn P Richard

Abstract

The role of the hydrophobic side chains of Ile-172 and Leu-232 in catalysis of the reversible isomerization of R-glyceraldehyde 3-phosphate (GAP) to dihydroxyacetone phosphate (DHAP) by triosephosphate isomerase (TIM) from Trypanosoma brucei brucei (Tbb) has been investigated. The I172A and L232A mutations result in 100- and 6-fold decreases in k(cat)/K(m) for the isomerization reaction, respectively. The effect of the mutations on the product distributions for the catalyzed reactions of GAP and of [1-(13)C]-glycolaldehyde ([1-(13)C]-GA) in D(2)O is reported. The 40% yield of DHAP from wild-type Tbb TIM-catalyzed isomerization of GAP with intramolecular transfer of hydrogen is found to decrease to 13% and to 4%, respectively, for the reactions catalyzed by the I172A and L232A mutants. Likewise, the 13% yield of [2-(13)C]-GA from isomerization of [1-(13)C]-GA in D(2)O is found to decrease to 2% and to 1%, respectively, for the reactions catalyzed by the I172A and L232A mutants. The decrease in the yield of the product of intramolecular transfer of hydrogen is consistent with a repositioning of groups at the active site that favors transfer of the substrate-derived hydrogen to the protein or the oxygen anion of the bound intermed...Continue Reading

References

May 29, 1991·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·J R Knowles
Mar 14, 1991·Nature·J R Knowles
May 8, 1990·Biochemistry·I A RoseJ V Warms
Apr 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·D StrausW Gilbert
Sep 1, 1972·The Biochemical Journal·B Plaut, J R Knowles
Jun 26, 1981·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·T AlberI A Wilson
Jan 2, 2003·Proceedings of the National Academy of Sciences of the United States of America·Gerwald JoglLiang Tong
Jan 11, 2003·The Journal of Biological Chemistry·Inari Kursula, Rik K Wierenga
Jun 26, 2003·Nucleic Acids Research·Elisabeth GasteigerAmos Bairoch
May 29, 2004·Protein Engineering, Design & Selection : PEDS·I KursulaR K Wierenga
Dec 21, 2006·Biochemistry·Marco G CasteleijnRik K Wierenga
Apr 12, 2007·IUBMB Life·Ferene OroszJudit Ovádi
Sep 30, 2009·Biochimica Et Biophysica Acta·Ferenc OroszJudit Ovádi
Aug 10, 2010·Cellular and Molecular Life Sciences : CMLS·R K WierengaR Venkatesan
Sep 9, 2010·Journal of the American Chemical Society·Maybelle K GoJohn P Richard
Oct 19, 2010·Current Opinion in Structural Biology·M Merced MalabananJohn P Richard

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Citations

Apr 9, 2013·Journal of the American Chemical Society·M Merced MalabananJohn P Richard
Nov 28, 2013·Journal of the American Chemical Society·Krisztina SpongJohn P Richard
Jan 19, 2013·Biochemistry·Tina L Amyes, John P Richard
Jun 25, 2014·Journal of the American Chemical Society·Lawrence M GoldmanJohn P Richard
Apr 5, 2014·Current Opinion in Chemical Biology·John P RichardXiang Zhai
Jul 8, 2017·Journal of the American Chemical Society·Yashraj S KulkarniShina C L Kamerlin
Dec 3, 2016·Protein Engineering, Design & Selection : PEDS·T L AmyesJ P Richard
Oct 28, 2019·Biochemical Society Transactions·Cátia MoreiraShina Caroline Lynn Kamerlin
Sep 29, 2017·Organic & Biomolecular Chemistry·Archie C ReyesJohn P Richard
May 4, 2021·Accounts of Chemical Research·John P RichardTina L Amyes
Feb 1, 2019·Journal of the American Chemical Society·John P Richard
Apr 24, 2019·The Journal of Physical Chemistry. B·Hua DengRobert Callender
Nov 27, 2018·Journal of the American Chemical Society·Archie C ReyesJohn P Richard
Nov 17, 2015·Journal of the American Chemical Society·Xiang ZhaiJohn P Richard

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