R. Eliasson et al., ALLOSTERIC REGULATION OF THE 3RD RIBONUCLEOTIDE REDUCTASE (NRDEF ENZYME) FROM ENTEROBACTERIACEAE, The Journal of biological chemistry, 271(43), 1996, pp. 26582-26587
Enterobacteriaceae contain genes for three separate ribonucleotide red
uctases: nrdAB code for a class Ia enzyme, active during aerobiosis, n
rdDG for a class III enzyme, active during anaerobiosis, and nrdEF for
a cryptic class Ib enzyme, The NrdEF enzyme provides the active reduc
tase in other, widely different bacteria, Here, we describe the allost
eric regulation of the Salmonella, typhimurium NrdEF enzyme, It consis
ts of two tightly bound homodimeric proteins, R1E and R2F. Nucleoside
triphosphates (ATP, dATP, dGTP, and dTTP) regulate the substrate speci
ficity by binding to a single site af the R1E protein (one nucleotide
per polypeptide). Regulation is similar to that of the NrdAB enzyme, w
ith one major exception: dATP stimulates reduction of CDP (and UDP) un
der conditions when dATP strongly inhibits all activity of the NrdAB e
nzyme. The nrdA-coded RI protein contains a second binding site for dA
TP (and ATP) that controls general enzyme activity, All known R1E prot
eins lack tile 50 N-terminal amino acids of R1, and we propose that th
e activity site is located ill this area of the protein, The more soph
isticated regulation of NrdAB enzymes of eukaryotes provides protectio
n against the possibly harmful overproduction of dNTPs.