Cicero D O, Barbato G, Koch U, Ingallinella P, Bianchi E, Nardi M C, Steinkühler C, Cortese R, Matassa V, De Francesco R, Pessi A, Bazzo R
Istituto di Ricerche di Biologia Molecolare P. Angeletti (IRBM), via Pontina Km 30.600, Pomezia (Rome), 00040, Italy.
J Mol Biol. 1999 Jun 4;289(2):385-96. doi: 10.1006/jmbi.1999.2746.
The interactions of peptide inhibitors, obtained by the optimization of N-terminal cleavage products of natural substrates, with the protease of human hepatitis C virus (HCV) are characterized by NMR and modelling studies. The S-binding region of the enzyme and the bound conformation of the ligands are experimentally determined. The NMR data are then used as the experimental basis for modelling studies of the structure of the complex. The S-binding region involves the loop connecting strands E2 and F2, and appears shallow and solvent-exposed. The ligand binds in an extended conformation, forming an antiparallel beta-sheet with strand E2 of the protein, with the P1 carboxylate group in the oxyanion hole.
通过对天然底物的N端裂解产物进行优化得到的肽抑制剂与人丙型肝炎病毒（HCV）蛋白酶之间的相互作用，通过核磁共振（NMR）和建模研究进行了表征。实验确定了该酶的S结合区域以及配体的结合构象。然后，将NMR数据用作复合物结构建模研究的实验基础。S结合区域涉及连接链E2和F2的环，看起来较浅且暴露于溶剂中。配体以伸展构象结合，与蛋白质的链E2形成反平行β-折叠，P1羧基位于氧负离子洞中。
