Thiopurine methyltransferase

• OMIM: 187 680
• UniProt: P51580
• MGI: 98812

Thiopurine methyltransferase ( Syn.Thiopurin -S- methyltransferase, mercaptopurine methyltransferase, 6 - thiopurine transmethylase, TPMT ) is an enzyme in the cytosol of animals, fungi and bacteria, which is methylated thiopurines. This reaction is part of the biotransformation of exogenous substances and a rare deficiency of the enzyme in humans leads to the fact that drugs that contain thiopurines ( azathioprine and 6TG ), act in a normal dose as a poison.

Catalyzed reaction

S- adenosylmethionine and thiopurine be converted to S- adenosyl -L- homocysteine ​​and thiopurine S- methyl ether. The enzyme is inhibited by S- adenosyl-L- homocysteine.

Structure

TPMT is a monomeric, consisting of a protein domain with 9 -piece core ( β -sheet structure ) embedded in 2α helices. The complete co- product S -adenosyl- homocysteine ​​(SAH ) binds to various areas ( α1, α5, α6 ), and is at the β -sheet structure 1 and 2 S- adenosyl- homocysteine ​​bound by the α1 -helix in the enzyme which contains the active site.

Function

The thiopurine azathioprine metabolized in the organism. If a deficiency of this enzyme exists, it may be caused by accumulation of degradation products of Azathioprins to increased side effects.

Proof

The thiopurine methyltransferase is determined in a radiochemical assay.