The relationships between transketolase, yeast pyruvate decarboxylase and pyruvate dehydrogenase of the pyruvate dehydrogenase complex.
The amino acid sequences of four thiamine pyrophosphate-requiring enzymes were aligned with the published amino acid sequence of the transketolase of Hansenula polymorpha. Sequences of the combined alpha and beta subunits of the E1 enzyme of the pyruvate dehydrogenase complexes of Homo sapiens and Bacillus stearothermophilus aligned well with the transketolase while the E1 of the pyruvate dehydrogenase complex of Escherichia coli aligned easily provided a non-aligning segment of 77 amino acids was omitted. The non-acetylating pyruvate decarboxylase of Saccharomyces cerevisiae could only be aligned if the sequence was cut in two with the C-terminus corresponding to the N-terminus of the other TPP-dependent enzymes. Using the published 2.5 A resolution of the X-ray crystal structure of Saccharomyces cerevisiae transketolase as a template we show that a hydrophobic region of the beta-subunit of the PDH E1 alpha beta enzymes likely contains a binding site for the thiazolium ring of TPP and key motifs are retained in common by all the TPP-dependent enzymes considered, which are essential for catalysis.
Robinson
B H
BH
Department of Biochemistry, Hospital for Sick Children, Toronto, Ont., Canada.
Chun
K
K
D000595:Amino Acid Sequence; D001665:Binding Sites; D006801:Humans; D008969:Molecular Sequence Data; D010843:Pichia / Q000201:enzymology; D011767:Pyruvate Decarboxylase / Q000235:genetics* / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D013835:Thiamine Pyrophosphate / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D014174:Transketolase / Q000235:genetics* / Q000378:metabolism
D011768:Pyruvate Dehydrogenase Complex; D013844:Thiazoles; D014174:Transketolase; D011767:Pyruvate Decarboxylase; D013835:Thiamine Pyrophosphate