A thiamin diphosphate binding fold revealed by comparison of the crystal structures of transketolase, pyruvate oxidase and pyruvate decarboxylase.
BACKGROUND
The crystal structures of three thiamin diphosphate-dependent enzymes that catalyze distinct reactions in basic metabolic pathways are known. These enzymes--transketolase, pyruvate oxidase and pyruvate decarboxylase--also require metal ions such as Ca2+ and Mg2+ as cofactors and have little overall sequence similarity. Here, the crystal structures of these three enzymes are compared.


RESULTS
The three enzymes share a similar pattern of binding of thiamin diphosphate and the metal ion cofactors. The enzymes function as multisubunit proteins, with each polypeptide chain folded into three alpha/beta domains. Two of these domains are involved in binding of the thiamin diphosphate and the metal ion. These domains have the same topology of six parallel beta-strands and surrounding alpha-helices. The thiamin diphosphate is bound in a cleft, formed by two domains from two different subunits. Only a few residues are conserved in all three enzymes and these are responsible for proper binding of the cofactors.


CONCLUSIONS
Despite considerable differences in quaternary structure and lack of overall sequence homology, thiamin diphosphate binds to the three enzymes in a very similar fashion, and a general thiamin-binding fold can be revealed.
Muller
Y A
YA
Institut für Organische Chemie und Biochemie, Albert-Ludwigs-Universität, Freiburg im Breisgau, Germany.
Lindqvist
Y
Y
Furey
W
W
Schulz
G E
GE
Jordan
F
F
Schneider
G
G
D000595:Amino Acid Sequence; D001665:Binding Sites; D003196:Computer Graphics; D018360:Crystallography, X-Ray / Q000379:methods; D007778:Lactobacillus / Q000201:enzymology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011767:Pyruvate Decarboxylase / Q000737:chemistry* / Q000378:metabolism; D011771:Pyruvate Oxidase / Q000737:chemistry* / Q000378:metabolism; D012440:Saccharomyces / Q000201:enzymology; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D017386:Sequence Homology, Amino Acid; D013835:Thiamine Pyrophosphate / Q000378:metabolism*; D014174:Transketolase / Q000737:chemistry* / Q000378:metabolism
D011771:Pyruvate Oxidase; D014174:Transketolase; D011767:Pyruvate Decarboxylase; D013835:Thiamine Pyrophosphate