3LXO

The crystal structure of ribonuclease A in complex with thymidine-3'-monophosphate

3LXO の概要

• エントリーDOI: 10.2210/pdb3lxo/pdb
• 分子名称: Ribonuclease pancreatic, THYMIDINE-3'-PHOSPHATE (3 entities in total)
• 機能のキーワード: ribonuclease a, rna cleavage, nucleotides, enzyme catalysis, inhibitors, disulfide bond, endonuclease, glycation, glycoprotein, hydrolase, nuclease, secreted
• 由来する生物種: Bos taurus (bovine,cow,domestic cattle,domestic cow)
• 細胞内の位置: Secreted: P61823
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 14030.53

構造登録者

Doucet, N.,Jayasundera, T.B.,Simonovic, M.,Loria, J.P. (登録日: 2010-02-25, 公開日: 2010-04-28, 最終更新日: 2024-10-16)

主引用文献

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

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: 20602460
DOI: 10.1002/prot.22754

実験手法

X-RAY DIFFRACTION (1.549 Å)