Protein Name

Pyruvate dehydrogenase complex


Geobacillus stearothermophilus (bacteria,thermophile)

Biological Context

In the beginning of the 19-th century an unknown disease was taking its tolls on mankind. Strangely, it was affecting only people who were eating polished rice. Those who boiled it with the husk did not show any of the symptoms, e.g. burning sensation of the feet, calf muscle tenderness and cramps, difficulty in rising from a squatting position, a decrease in the vibratory sensation in the toes, loss of ankle and knee jerks etc. The chemist Casimir Funk assumed that probably the rice husks contained a vital compound a shortage of which in the food would cause the development of beriberi. Finally he managed to extract an amine and called it "vitamin", short for "vital amine". Later it was realized that the substance that Funk has discovered was not the one curing beriberi. Anyway, the name was kept and the new compound was called Vitamin B1. Scientists often refer to it as thiamin or aneurin. Vitamin B1, or thiamin, is a water soluble base, consisting of substituted pyrimidine connected to a substituted thiazole ring. Food supplements do not contain the pure vitamin, but its salts thiamin hydrochloride or thiamin mononitrate . In the body, they are converted into the active coenzyme form, the thiamin pyrophosphate, TPP . It is also known as thiamin diphosphate, TDP, and cocarboxylase . Thiamin diphosphate plays a crucial role in numerous metabolic reactions, some of the more important ones being the oxidative decarboxylation of pyruvate to acetyl CoA, and alphaketoglutarate to succinyl CoA in the Krebs cycle, the energy "power station" of the cells. The conversion of pyruvate to acetyl CoA is catalyzed by a multiprotein assembly called Pyruvate Dehydrogenase Complex. In this complex , TPP is the cofactor for the pyruvate dehydrogenase component of the complex, also called E1.

Structure Description


Here we can see the structure of E1 bound to the peripheral subunit-binding domain (PSBD) in B. stearothermophilus. The structure includes two TPP molecules bound at each active site, and three Mg+ ions - one per active site, and one at the center of the E1 tetramer. A tunnel rich in acidic residues connects the two active sites. After the first thiamin pyrophosphate binds, it releases a proton, and converts into a TPP carbanion. This is the active form of the molecule. The released proton uses the acidic tunnel as a "highway", or usually called "proton wire", to reach the other active site, some 20A away. The release of the proton is accompanied by the rearrangement of two loops near the TPP molecule and closure of the site. On the other end of the tunnel a second TPP is bound. But the proton from the first one prevents it from releasing its own, so it stays dormant. The activated TPP at the first site then binds a substrate molecule, pyruvate. Decarboxylation of the pyruvate requires a proton , kindly provided by the second TPP . In this "ping-pong" fashion, the second TPP is also activated and ready for the next pyruvate molecule. Another example of how elegant Nature is .

Protein Data Bank (PDB)



  • Frank, R.A.W. Titman, C.M. Pratap, J.V. Luisi, B.F. Perham, R.N.; "A Molecular Switch and Proton Wire Synchronize the Active Sites in Thiamine Enzymes"; Science; (2004) 306:872-876 PubMed:15514159.


author: Rossen Apostolov

Japanese version:PDB:1W85