PDBsum entry 1l1l

Oxidoreductase

PDB id: 1l1l

Contents

Protein chains

717 a.a. *

Waters ×2875

* Residue conservation analysis

References listed in PDB file

Key reference

Title

The crystal structure of class ii ribonucleotide reductase reveals how an allosterically regulated monomer mimics a dimer.

Authors

M.D.Sintchak, G.Arjara, B.A.Kellogg, J.Stubbe, C.L.Drennan.

Ref.

Nat Struct Biol, 2002, 9, 293-300. [DOI no: 10.1038/nsb774]

PubMed id

11875520

Abstract

Ribonucleotide reductases (RNRs) catalyze the conversion of ribonucleotides to deoxyribonucleotides, an essential step in DNA biosynthesis and repair. Here we present the crystal structure of class II (coenzyme B12-dependent) ribonucleoside triphosphate reductase (RTPR) from Lactobacillus leichmannii in the apo enzyme form and in complex with the B12 analog adeninylpentylcobalamin at 1.75 and 2.0 A resolution, respectively. This monomeric, allosterically regulated class II RNR retains all the key structural features associated with the catalytic and regulatory machinery of oligomeric RNRs. Surprisingly, the dimer interface responsible for effector binding in class I RNR is preserved through a single 130-residue insertion in the class II structure. Thus, L. leichmannii RNR is a paradigm for the simplest structural entity capable of ribonucleotide reduction, a reaction linking the RNA and DNA worlds.

Figure 1.
Figure 1. General reaction catalyzed by ribonucleotide reductases. Each of the three well-characterized RNR classes uses a different metallocofactor to generate the thiyl radical (S ). For class II RNRs, the S (Cys 408 in L. leichmannii) is generated by AdoCbl carbon-cobalt (C -Co) bond homolysis. Hydrogen atom (red) abstraction from the substrate by the thiyl radical and the subsequent multiple step radical rearrangements result in the loss of the 2' hydroxyl group in the form of water. In class I and II RNRs, reducing equivalents for the reaction are provided by the oxidation of two Cys residues to a disulfide (Cys 119 -Cys 419 in L. leichmannii)35. In contrast, class III RNR obtains reducing equivalents by the oxidation of formate^36.

Figure 4.
Figure 4. B[12] bound to RNR. a, Chemical structures of adenosylcobalamin (AdoCbl, left panel) and adeninylpentylcobalamin (AdPentCbl, right panel). b, Difference (F[o] - F[c]) electron density at 2.0 Å resolution (2 contour) for AdPentCbl bound to L. leichmannii RTPR, calculated before the inclusion of any AdPentCbl atoms in the refinement. The orientation of AdPentCbl in (b) is the same as in (a). Figure prepared using Ribbons37.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2002, 9, 293-300) copyright 2002.