Specificity and genetics of S-adenosylmethionine transport in Saccharomyces cerevisiae.
The specificity of a transport system for S-adenosylmethionine was determined through the use of structurally related derivatives. Of the compounds tested, the analogues S-adenosylethionine and S-inosylmethionine and the naturally occurring compounds S-adenosyl-(5')-3-methylthiopropylamine and S-adenosylhomocysteine competitively inhibited uptake of the sulfonium compound. Ki values for these compounds indicate that the order of affinity for the transport protein is S-adenosylmethionine congruent to S-adenosyl-(5')-3-methyl-thiopropylamine greater than S-adenosylethionine greater than S-inosylmethionine greater than S-adenosylhomocysteins. S-adenosyl-(2-hydroxy-4-methylthio)butyric acid exerted inhibition of a mixed type. S-insoyl-(2-hydroxy-4-methylthio)butyric acid, S-inosylhomocysteine, and S-ribosylhomocysteine were without effect. On the basis of the inhibition data, the methionine-amino, adenine-amino, and methyl groups were identified as group important in the binding of S-adenosylmethionine to the transport protein. Comparison is made with the specificities of various transmethylating enzymes utilizing S-adenosylmethionine. In addition, a number of conventional and temperature-sensitive S-adenosylmethionine transport mutants were isolated and analyzed in an attempt to identify the structural character of the specific transport protein(s). The data obtained suggest that only a single gene (a single polypeptide) is involved in specific S-adenosylmethionine transport. Apparent interallelic complementation supports the assumption that the functional form of the protein is composed of two or more copies of a monomer.
D001426:Bacterial Proteins / Q000032:analysis; D001665:Binding Sites; D001667:Binding, Competitive; D001693:Biological Transport, Active; D005001:Ethionine / Q000378:metabolism; D005796:Genes; D008040:Genetic Linkage; D006710:Homocysteine / Q000378:metabolism; D007700:Kinetics; D009154:Mutation; D011487:Protein Conformation; D012436:S-Adenosylmethionine / Q000031:analogs & derivatives / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D013329:Structure-Activity Relationship
D001426:Bacterial Proteins; D006710:Homocysteine; D012436:S-Adenosylmethionine; D005001:Ethionine