4ERP
Crystal structure of a gemcitabine-diphosphate inhibited E. coli class Ia ribonucleotide reductase complex
Summary for 4ERP
| Entry DOI | 10.2210/pdb4erp/pdb |
| Related | 4ERM |
| Descriptor | Ribonucleoside-diphosphate reductase 1 subunit alpha, Ribonucleoside-diphosphate reductase 1 subunit beta, ADENOSINE-5'-TRIPHOSPHATE, ... (5 entities in total) |
| Functional Keywords | protein-protein complex, alpha/beta barrel, atp cone, diiron center, oxidoreductase, rnr alpha, rnr beta, thioredoxin, ribonucleotide reduction, cytosol |
| Biological source | Escherichia coli K-12 More |
| Total number of polymer chains | 8 |
| Total formula weight | 519755.28 |
| Authors | Zimanyi, C.M.,Drennan, C.L. (deposition date: 2012-04-20, release date: 2012-07-04, Last modification date: 2023-09-13) |
| Primary citation | Zimanyi, C.M.,Ando, N.,Brignole, E.J.,Asturias, F.J.,Stubbe, J.,Drennan, C.L. Tangled up in knots: structures of inactivated forms of E. coli class Ia ribonucleotide reductase. Structure, 20:1374-1383, 2012 Cited by PubMed Abstract: Ribonucleotide reductases (RNRs) provide the precursors for DNA biosynthesis and repair and are successful targets for anticancer drugs such as clofarabine and gemcitabine. Recently, we reported that dATP inhibits E. coli class Ia RNR by driving formation of RNR subunits into α4β4 rings. Here, we present the first X-ray structure of a gemcitabine-inhibited E. coli RNR and show that the previously described α4β4 rings can interlock to form an unprecedented (α4β4)2 megacomplex. This complex is also seen in a higher-resolution dATP-inhibited RNR structure presented here, which employs a distinct crystal lattice from that observed in the gemcitabine-inhibited case. With few reported examples of protein catenanes, we use data from small-angle X-ray scattering and electron microscopy to both understand the solution conditions that contribute to concatenation in RNRs as well as present a mechanism for the formation of these unusual structures. PubMed: 22727814DOI: 10.1016/j.str.2012.05.009 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (4.45 Å) |
Structure validation
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