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ribonucleotide reductase
Function:
- glutathione reductase-dependent reduction of ribonuclotides
- catalyzes biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides
- glutaredoxin functions as an electron carrier
- provides precursors for DNA synthesis
- DNA replication
- DNA repair
2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O
ribonucleoside diphosphate + thioredoxin
Cofactor: binds 2 Fe+2/Fe+3 per subunit (putative)
Structure:
- heterodimer of a large (B1) & a small chain (B2)
- 2 distinct regulatory sites have been defined:
a) specificity site, which controls substrate specificity
b) activity site which regulates overall catalytic activity
- substrate-binding catalytic site, located on B1, is formed only in the presence of the second subunit B2
Compartment: cytoplasm
Pathology:
- ribonucleotide reductase is thought to mediate pathogenesis of the immunodeficiency of
a) adenosine deaminase deficiency
b) purine nucleoside phosphorylase deficiency
- deoxynucleotides that accumulate in lymphoid cells are thought to feed-back inhibit ribonucleotide reductase, preventing DNA replication & cell proliferation
Specific
ribonucleotide diphosphate reductase
General
multisubunit protein
nuclear protein
oxidoreductase
Properties
COMPARTMENT: cell nucleus
MOTIF: active site
SUBUNITS: ribonucleotide reductase B1
MOTIF: ATP-cone {1-92}
cysteine residue {C218}
Allosteric effector binding {226-226}
Allosteric effector binding {256-256}
asparagine residue {N427}
cysteine residue {C429}
glutamate residue {E431}
cysteine residue {C444}
tyrosine residue {Y737}
tyrosine residue {Y738}
thioredoxin interaction {787-787}
thioredoxin interaction {790-790}
ribonucleotide reductase B2
MOTIF: Ser phosphorylation site {S20}
Iron [Fe]-binding site
SITE: 138-138
Iron [Fe]-binding site
SITE: 169-169
Iron [Fe]-binding site
SITE: 172-172
tyrosine residue {Y176}
Iron [Fe]-binding site
SITE: 232-232
Iron [Fe]-binding site
SITE: 266-266
Iron [Fe]-binding site
SITE: 269-269
glutaredoxin
MOTIF: cysteine residue {C23}
MODIFICATION: cysteine residue {C26}
cysteine residue {C26}
MODIFICATION: cysteine residue {C23}
cysteine residue {C79}
MODIFICATION: cysteine residue {C83}
cysteine residue {C83}
MODIFICATION: cysteine residue {C79}
Database Correlations
ENZYME 1.17.4.1
References
- Stryer Biochemistry WH Freeman & Co, New York, 1988 pg 610
- PROSITE :accession PDOC00173
- PROSITE :accession PS00195}
Components
glutaredoxin (GLRX)
ribonucleotide reductase B1 subunit; M1 subunit; ribonucleoside diphosphate reductase large subunit (RRM1, RR1)
ribonucleotide reductase B2 subunit (M2 subunit, ribonucleotide reductase small subunit, RRM2, RR2)