3LXO
The crystal structure of ribonuclease A in complex with thymidine-3'-monophosphate
Summary for 3LXO
| Entry DOI | 10.2210/pdb3lxo/pdb |
| Descriptor | Ribonuclease pancreatic, THYMIDINE-3'-PHOSPHATE (3 entities in total) |
| Functional Keywords | ribonuclease a, rna cleavage, nucleotides, enzyme catalysis, inhibitors, disulfide bond, endonuclease, glycation, glycoprotein, hydrolase, nuclease, secreted |
| Biological source | Bos taurus (bovine,cow,domestic cattle,domestic cow) |
| Cellular location | Secreted: P61823 |
| Total number of polymer chains | 1 |
| Total formula weight | 14030.53 |
| Authors | Doucet, N.,Jayasundera, T.B.,Simonovic, M.,Loria, J.P. (deposition date: 2010-02-25, release date: 2010-04-28, Last modification date: 2024-10-16) |
| Primary citation | Doucet, N.,Jayasundera, T.B.,Simonovic, M.,Loria, J.P. The crystal structure of ribonuclease A in complex with thymidine-3'-monophosphate provides further insight into ligand binding. Proteins, 78:2459-2468, 2010 Cited by PubMed Abstract: Thymidine-3'-monophosphate (3'-TMP) is a competitive inhibitor analogue of the 3'-CMP and 3'-UMP natural product inhibitors of bovine pancreatic ribonuclease A (RNase A). Isothermal titration calorimetry experiments show that 3'-TMP binds the enzyme with a dissociation constant (K(d)) of 15 microM making it one of the strongest binding members of the five natural bases found in nucleic acids (A, C, G, T, and U). To further investigate the molecular properties of this potent natural affinity, we have determined the crystal structure of bovine pancreatic RNase A in complex with 3'-TMP at 1.55 A resolution and we have performed NMR binding experiments with 3'-CMP and 3'-TMP. Our results show that binding of 3'-TMP is very similar to other natural and non-natural pyrimidine ligands, demonstrating that single nucleotide affinity is independent of the presence or absence of a 2'-hydroxyl on the ribose moiety of pyrimidines and suggesting that the pyrimidine binding subsite of RNase A is not a significant contributor of inhibitor discrimination. Accumulating evidence suggests that very subtle structural, chemical, and potentially motional variations contribute to ligand discrimination in this enzyme. PubMed: 20602460DOI: 10.1002/prot.22754 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.549 Å) |
Structure validation
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