The UDP-glucuronosyltransferases as oligomeric enzymes.
The UDP-glucuronosyltransferases (UGTs) are integral membrane proteins of the endoplasmic reticulum that play important roles in the defense against potentially hazardous xenobiotics. The UGTs also participate in the metabolism and homeostasis of many endogenous compounds, including bilirubin and steroid hormones. Most human UGTs can glucuronidate several substrates the chemical structures of which may vary significantly. Understanding the structural basis for the complex substrate specificity of the UGTs is a major challenge that is hampered by the lack of sufficient structural information on these enzymes. Nevertheless, there is currently a broad interest in the structure and function of the UGTs and here we have focused on their oligomeric state. The question whether or not the UGTs are oligomeric enzymes, either dimeric or tetrameric, was frequently addressed in the past, as well as in recent studies. The current knowledge of protein-protein interactions among the UGTs is limited, however, primarily due to considerable difficulties in purifying individual recombinant UGTs as fully active and mono-dispersed proteins. Such hurdles in studying the oligomeric state of the UGTs prompted researchers to develop less direct approaches for examining the quaternary structure of the UGTs and its functional significance. In this article we have reviewed, sometimes critically, most of the available studies about the oligomeric state of the UGTs. Concluding that the UGTs are oligomeric enzymes, we discuss hetero-oligomerization among UGTs and its possible implications for the structure, function and substrate specificity of the enzymes.
Finel
Moshe
M
Drug Discovery and Development Technology Center (DDTC), University of Helsinki, Finland. moshe.finel@helsinki.fi
Kurkela
Mika
M
D001665:Binding Sites; D001704:Biopolymers; D002462:Cell Membrane / Q000201:enzymology; D019281:Dimerization; D014453:Glucuronosyltransferase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D011485:Protein Binding
D001704:Biopolymers; D014453:Glucuronosyltransferase