The crystal structure of class II ribonucleotide reductase reveals how an allosterically regulated monomer mimics a dimer.
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.
Sintchak
Michael D
MD
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Arjara
Gitrada
G
Kellogg
Brenda A
BA
Stubbe
JoAnne
J
Drennan
Catherine L
CL
D000494:Allosteric Regulation; D001051:Apoenzymes / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002384:Catalysis; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D019281:Dimerization; D019143:Evolution, Molecular; D005609:Free Radicals / Q000378:metabolism; D007778:Lactobacillus / Q000201:enzymology*; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000378:metabolism; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D012264:Ribonucleotide Reductases / Q000737:chemistry* / Q000145:classification / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013455:Sulfur / Q000378:metabolism
D001051:Apoenzymes; D005609:Free Radicals; D009942:Organometallic Compounds; C413930:adeninylpentylcobalamin; D013455:Sulfur; D012264:Ribonucleotide Reductases