PDBsum entry 2bq1

Oxidoreductase

PDB id: 2bq1

Contents

Protein chains

676 a.a. *

294 a.a. *

Ligands

DGT ×2

Metals

_MG ×2

_FE ×4

* Residue conservation analysis

PDB id:

2bq1

Name:

Oxidoreductase

Title:

Ribonucleotide reductase class 1b holocomplex r1e,r2f from salmonella typhimurium

Structure:

Ribonucleoside-diphosphate reductase 2 alpha subunit. Chain: e, f. Synonym: ribonucleotide reductase 2, r1e protein. Engineered: yes. Ribonucleoside-diphosphate reductase 2 beta subunit. Chain: i, j. Synonym: ribonucleotide reductase 2, r2f protein. Engineered: yes

Source:

Salmonella typhimurium. Organism_taxid: 602. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PDB file)

Resolution:

3.99Å R-factor: 0.265 R-free: 0.310

Authors:

M.Uppsten,M.Farnegardh,V.Domkin,U.Uhlin

Key ref:

M.Uppsten et al. (2006). The first holocomplex structure of ribonucleotide reductase gives new insight into its mechanism of action. J Mol Biol, 359, 365-377. PubMed id: 16631785 DOI: 10.1016/j.jmb.2006.03.035

Date:

26-Apr-05 Release date: 17-May-06

Protein chains

Q08698  (RIR3_SALTY) -  Ribonucleoside-diphosphate reductase 2 subunit alpha from Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)

Seq: 714 a.a.

Struc: 676 a.a.

Protein chains

P17424  (RIR4_SALTY) -  Ribonucleoside-diphosphate reductase 2 subunit beta from Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)

Seq: 319 a.a.

Struc: 294 a.a.

Enzyme reactions

• Enzyme class: Chains E, F, I, J: E.C.1.17.4.1 - ribonucleoside-diphosphate reductase.
• Reaction: a 2'-deoxyribonucleoside 5'-diphosphate + [thioredoxin]-disulfide + H2O = a ribonucleoside 5'-diphosphate + [thioredoxin]-dithiol
• Cofactor: Fe(3+) or adenosylcob(III)alamin or Mn(2+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.jmb.2006.03.035

J Mol Biol 359:365-377 (2006)

PubMed id: 16631785

The first holocomplex structure of ribonucleotide reductase gives new insight into its mechanism of action.

M.Uppsten, M.Färnegårdh, V.Domkin, U.Uhlin.

ABSTRACT

Ribonucleotide reductase is an indispensable enzyme for all cells, since it catalyses the biosynthesis of the precursors necessary for both building and repairing DNA. The ribonucleotide reductase class I enzymes, present in all mammals as well as in many prokaryotes and DNA viruses, are composed mostly of two homodimeric proteins, R1 and R2. The reaction involves long-range radical transfer between the two proteins. Here, we present the first crystal structure of a ribonucleotide reductase R1/R2 holocomplex. The biological relevance of this complex is based on the binding of the R2 C terminus in the hydrophobic cleft of R1, an interaction proven to be crucial for enzyme activity, and by the fact that all conserved amino acid residues in R2 are facing the R1 active sites. We suggest that the asymmetric R1/R2 complex observed in the 4A crystal structure of Salmonella typhimurium ribonucleotide reductase represents an intermediate stage in the reaction cycle, and at the moment of reaction the homodimers transiently form a tight symmetric complex.

Selected figure(s)

Figure 2.
Figure 2. The R2F protein. (a) The R2F dimer structure with the conserved side-chains and iron atoms highlighted. One monomer is in dark blue and the other is in blue-grey. Conserved side-chains are shown as yellow sticks. The iron atoms are shown as orange spheres. (b) The R2F iron-centre, with the iron atoms (orange) built into the electron density. The 2F[o]−F[c] density map contoured at 1.0σ (blue) and the F[o]−F[c] omit map contoured at 2.6σ (green). Figure 2. The R2F protein. (a) The R2F dimer structure with the conserved side-chains and iron atoms highlighted. One monomer is in dark blue and the other is in blue-grey. Conserved side-chains are shown as yellow sticks. The iron atoms are shown as orange spheres. (b) The R2F iron-centre, with the iron atoms (orange) built into the electron density. The 2F[o]−F[c] density map contoured at 1.0σ (blue) and the F[o]−F[c] omit map contoured at 2.6σ (green).

Figure 3.
Figure 3. The R1E protein. (a) The R1E dimer structure. The N-terminal domains are coloured in blue-green, the small domains in gold. The catalytic ten-stranded α/β barrel is coloured brown in one monomer and beige in the other. One hydrophobic cleft of R1E is marked (blue peptide) as well as the helices forming the cleft. The radical forming C388 at the active sites are marked as spheres coloured by atom. The dGTP effectors on each side of the dimer interface are shown in sticks. Three loops are marked. Flexible parts of the loops are indicated by broken lines. (b)The effector dGTP at the specificity site of R1E. In brown is the initial F[o]−F[c] electron density map contoured at 3.0σ and in light grey the final 2F[o]−F[c] density map contoured at 1.0σ. The loop shown in the picture, loop 1, is stabilised by the binding of the effector. The magnesium ion is colored magenta with the F[o]−F[c] omit map for the Mg in green (contoured at 3.0σ). Figure 3. The R1E protein. (a) The R1E dimer structure. The N-terminal domains are coloured in blue-green, the small domains in gold. The catalytic ten-stranded α/β barrel is coloured brown in one monomer and beige in the other. One hydrophobic cleft of R1E is marked (blue peptide) as well as the helices forming the cleft. The radical forming C388 at the active sites are marked as spheres coloured by atom. The dGTP effectors on each side of the dimer interface are shown in sticks. Three loops are marked. Flexible parts of the loops are indicated by broken lines. (b)The effector dGTP at the specificity site of R1E. In brown is the initial F[o]−F[c] electron density map contoured at 3.0σ and in light grey the final 2F[o]−F[c] density map contoured at 1.0σ. The loop shown in the picture, loop 1, is stabilised by the binding of the effector. The magnesium ion is colored magenta with the F[o]−F[c] omit map for the Mg in green (contoured at 3.0σ).

The above figures are reprinted by permission from Elsevier: J Mol Biol (2006, 359, 365-377) copyright 2006.

Figures were selected by an automated process.