4ZRO

2.1 A X-Ray Structure of FIPV-3CLpro bound to covalent inhibitor

4ZRO の概要

• エントリーDOI: 10.2210/pdb4zro/pdb
• 関連するBIRD辞書のPRD_ID: PRD_002174
• 分子名称: 3C-like proteinase, Bounded inhibitor of N-(tert-butoxycarbonyl)-L-seryl-L-valyl-N-{(2S)-5-ethoxy-5-oxo-1-[(3S)-2-oxopyrrolidin-3-yl]pentan-2-yl}-L-leucinamide, DIMETHYL SULFOXIDE, ... (4 entities in total)
• 機能のキーワード: coronavirus, main protease, 3clpro, mpro, fipv, fcov, inhibitor complex, feline infectious peritonitis, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Feline coronavirus (strain FIPV WSU-79/1146) (FCoV); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 133587.53

構造登録者

St John, S.E.,Mesecar, A.D. (登録日: 2015-05-12, 公開日: 2015-10-14, 最終更新日: 2025-04-02)

主引用文献

St John, S.E.,Therkelsen, M.D.,Nyalapatla, P.R.,Osswald, H.L.,Ghosh, A.K.,Mesecar, A.D.
X-ray structure and inhibition of the feline infectious peritonitis virus 3C-like protease: Structural implications for drug design.
Bioorg.Med.Chem.Lett., 25:5072-5077, 2015

PubMed Abstract: Feline infectious peritonitis (FIP) is a deadly disease that effects both domestic and wild cats and is caused by a mutation in feline coronavirus (FCoV) that allows the virus to replicate in macrophages. Currently, there are no treatments or vaccines available for the treatment of FIP even though it kills approximately 5% of cats in multi-cat households per year. In an effort to develop small molecule drugs targeting FIP for the treatment of cats, we screened a small set of designed peptidomimetic inhibitors for inhibition of FIPV-3CL(pro), identifying two compounds with low to sub-micromolar inhibition, compound 6 (IC50=0.59±0.06 μM) and compound 7 (IC50=1.3±0.1 μM). We determined the first X-ray crystal structure of FIPV-3CL(pro) in complex with the best inhibitor identified, compound 6, to a resolution of 2.10 Å to better understand the structural basis for inhibitor specificity. Our study provides important insights into the structural requirements for the inhibition of FIPV-3CL(pro) by peptidomimetic inhibitors and expands the current structural knowledge of coronaviral 3CL(pro) architecture.

PubMed: 26592814
DOI: 10.1016/j.bmcl.2015.10.023

実験手法

X-RAY DIFFRACTION (2.0566 Å)