TY - JOUR
T1 - Substrate specificity of glycinamide ribonucleotide transformylase from chicken liver
AU - Antle, Vincent D.
AU - Liu, Dashan
AU - McKellar, B. Robert
AU - Caperelli, Carol A.
AU - Hua, Mei
AU - Vince, Robert
PY - 1996/3/15
Y1 - 1996/3/15
N2 - Several glycinamide ribonucleotide analogs have been prepared and evaluated as substrates and/or inhibitors of glycinamide ribonucleotide transformylase from chicken liver. The side chain modified analogs, in which the glycine side chain, R = CH2NH2, has been replaced by R = CH2NHCH3 and R = CH2CH2NH2, are substrates, with V/K (relative intensity) of 2.4% and 16.3%, respectively. Several carbocyclic analogs of glycinamide ribonucleotide, including the phosphonate derivative of carbocyclic glycinamide ribonucleotide, did not serve as substrates, but were inhibitors of the enzyme, competitive against glycinamide ribonucleotide, with K(i) values ranging from 7.4 to 23.6 times the K(m) for glycinamide ribonucleotide. However, the O-phosphonate analog of carbocyclic glycinamide ribonucleotide did support enzymatic activity, with V/K (relative intensity) of 0.8%. In addition, glycinamide ribonucleoside was neither a substrate for, nor an inhibitor of, glycinamide ribonucleotide transformylase. Furthermore, α-glycinamide ribonucleotide had no effect on enzyme activity. These studies have begun to define the structural features of the nucleotide substrate required to support enzymatic activity.
AB - Several glycinamide ribonucleotide analogs have been prepared and evaluated as substrates and/or inhibitors of glycinamide ribonucleotide transformylase from chicken liver. The side chain modified analogs, in which the glycine side chain, R = CH2NH2, has been replaced by R = CH2NHCH3 and R = CH2CH2NH2, are substrates, with V/K (relative intensity) of 2.4% and 16.3%, respectively. Several carbocyclic analogs of glycinamide ribonucleotide, including the phosphonate derivative of carbocyclic glycinamide ribonucleotide, did not serve as substrates, but were inhibitors of the enzyme, competitive against glycinamide ribonucleotide, with K(i) values ranging from 7.4 to 23.6 times the K(m) for glycinamide ribonucleotide. However, the O-phosphonate analog of carbocyclic glycinamide ribonucleotide did support enzymatic activity, with V/K (relative intensity) of 0.8%. In addition, glycinamide ribonucleoside was neither a substrate for, nor an inhibitor of, glycinamide ribonucleotide transformylase. Furthermore, α-glycinamide ribonucleotide had no effect on enzyme activity. These studies have begun to define the structural features of the nucleotide substrate required to support enzymatic activity.
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U2 - 10.1074/jbc.271.11.6045
DO - 10.1074/jbc.271.11.6045
M3 - Article
C2 - 8626389
AN - SCOPUS:0029960034
SN - 0021-9258
VL - 271
SP - 6045
EP - 6049
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 11
ER -