Conserved residues are functionally distinct within transketolases of different species

Biochemistry
C K SingletonP R Martin

Abstract

Most of the amino acid residues which interact with thiamine pyrophosphate are highly conserved among enzymes which use this cofactor. The possible roles of several such residues in cofactor binding, catalysis, and/or substrate binding were examined for human transketolase. Mutations in H110 resulted in dramatic reductions to 2% or less of the normal activity. No alterations were found in the K(m)app's for the cofactor or for the donor and acceptor substrates. Alterations in Q428 resulted in a less severe loss of activity and also no changes in the K(m)app's. On the basis of the results, H110, an invariant residue, is proposed to function as a base which abstracts a proton from the protonated 4'-iminopyrimidine ring. The deprotonated 4'-imino moiety is required for generation of the C2-thiazolium carbanion which attacks the donor substrate. Interestingly, the function in the human enzyme of this invariant histidine is distinct from its role in yeast transketolase in which it aids in binding donor substrate and in subsequent catalytic events. Q428 is suggested to play a supportive role by stabilizing and orientating a water molecule which mediates the interaction between the 4'-amino group and H110. In other TPP-utilizing enzyme...Continue Reading

References

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Citations

Jun 5, 1998·The International Journal of Biochemistry & Cell Biology·G SchenkP F Nixon
Jan 30, 1999·The International Journal of Biochemistry & Cell Biology·G SchenkP F Nixon
Jul 30, 2010·The Journal of Biological Chemistry·Lars MitschkeKai Tittmann
Jun 1, 1997·Alcoholism, Clinical and Experimental Research·J J WangC K Singleton
Feb 1, 2011·Eukaryotic Cell·Robert L BowmanCharles K Singleton
Aug 3, 2010·Biochemistry. Biokhimii︠a︡·L E MeshalkinaG A Kochetov
Nov 16, 2011·Biochemistry. Biokhimii︠a︡·L E MeshalkinaG A Kochetov
Apr 16, 1998·FEBS Letters·U NilssonG Schneider
Oct 18, 2005·Biochimica Et Biophysica Acta·Malea M KneenMichael J McLeish
Sep 16, 1999·Archives of Biochemistry and Biophysics·L G KorotchkinaM S Patel
Jan 17, 2019·BMC Structural Biology·Gaurang P DeshpandeM Faadiel Essop

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