1XJF

Structural mechanism of allosteric substrate specificity in a ribonucleotide reductase: dATP complex

Summary for 1XJF

• Entry DOI: 10.2210/pdb1xjf/pdb
• Related: 1XJE 1XJG 1XJJ 1XJK 1XJM 1XJN
• Descriptor: ribonucleotide reductase, B12-dependent, MAGNESIUM ION, 2'-DEOXYADENOSINE 5'-TRIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: ribonucleotide reductase, 10 alpha-beta barrel, allosteric regulation, substrate specificity, protein-nucleotide complex, oxidoreductase
• Biological source: Thermotoga maritima
• Total number of polymer chains: 2
• Total formula weight: 147779.44

Authors

Larsson, K.-M.,Jordan, A.,Eliasson, R.,Reichard, P.,Logan, D.T.,Nordlund, P. (deposition date: 2004-09-23, release date: 2005-12-20, Last modification date: 2023-08-23)

Primary citation

Larsson, K.-M.,Jordan, A.,Eliasson, R.,Reichard, P.,Logan, D.T.,Nordlund, P.
Structural mechanism of allosteric substrate specificity regulation in a ribonucleotide reductase.
Nat.Struct.Mol.Biol., 11:1142-1149, 2004

PubMed Abstract: Ribonucleotide reductases (RNRs) catalyze the reduction of ribonucleotides into deoxyribonucleotides, which constitute the precursor pools used for DNA synthesis and repair. Imbalances in these pools increase mutational rates and are detrimental to the cell. Balanced precursor pools are maintained primarily through the regulation of the RNR substrate specificity. Here, the molecular mechanism of the allosteric substrate specificity regulation is revealed through the structures of a dimeric coenzyme B12-dependent RNR from Thermotoga maritima, both in complexes with four effector-substrate nucleotide pairs and in three complexes with only effector. The mechanism is based on the flexibility of loop 2, a key structural element, which forms a bridge between the specificity effector and substrate nucleotides. Substrate specificity is achieved as different effectors and their cognate substrates stabilize specific discrete loop 2 conformations. The mechanism of substrate specificity regulation is probably general for most class I and class II RNRs.

PubMed: 15475969
DOI: 10.1038/nsmb838

Experimental method

X-RAY DIFFRACTION (2.4 Å)