,
Crystal structure of the di-iron/radical protein of ribonucleotide reductase from Corynebacterium ammoniagenes.
Biochemistry, 41 (4): 1381--1389 (января 2002)
Аннотация
Ribonucleotide reductase (RNR) is the enzyme performing de novo production
of the four deoxyribonucleotides needed for DNA synthesis. All mammals
as well as some prokaryotes express the class I enzyme which is
an alpha(2)beta(2) protein. The smaller of the homodimers, denoted
R2, contains a di-iron carboxylate site which, upon reaction with
molecular oxygen, generates a stable tyrosyl radical needed for
catalysis. The three-dimensional structure of the oxidized class
Ib RNR R2 from Corynebacterium ammoniagenes has been determined
at 1.85 A resolution and refined to an R-value of 15.8% (R(free)
= 21.3%). In addition, structures of both the reduced iron-containing,
and manganese-substituted protein have been solved. The C. ammoniagenes
R2 has been proposed to be manganese-dependent. The present structure
provides evidence that manganese is not oxidized by the protein,
in agreement with recent biochemical data, and that no obvious structural
abnormalities are seen in the oxidized and reduced iron-containing
forms, giving further support that the protein is indeed an iron-dependent
RNR R2. The di-manganese structure also provides an explanation
for the magnetic properties of this site. The structure of the oxidized
C. ammoniagenes R2 also reveals an additional water molecule bridging
the radical and the iron site, which has not previously been seen
in any other R2 structure and which might have important mechanistic
implications.
