7Q8H

Peptide EVCKKKK in complex with human cathepsin V C25A mutant

これはPDB形式変換不可エントリーです。

7Q8H の概要

• エントリーDOI: 10.2210/pdb7q8h/pdb
• 分子名称: Cathepsin L2, EVCKKKK Peptide, (4S)-2-METHYL-2,4-PENTANEDIOL, ... (7 entities in total)
• 機能のキーワード: cathepsinv, peptidyl substrate, hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 51090.81

構造登録者

Loboda, J.,Sosnowski, P.,Tusar, L.,Vidmar, R.,Vizovisek, M.,Horvat, J.,Kosec, G.,Impens, F.,Demol, H.,Turk, B.,Gevaert, K.,Turk, D. (登録日: 2021-11-11, 公開日: 2022-11-23, 最終更新日: 2024-10-16)

主引用文献

Tusar, L.,Loboda, J.,Impens, F.,Sosnowski, P.,Van Quickelberghe, E.,Vidmar, R.,Demol, H.,Sedeyn, K.,Saelens, X.,Vizovisek, M.,Mihelic, M.,Fonovic, M.,Horvat, J.,Kosec, G.,Turk, B.,Gevaert, K.,Turk, D.
Proteomic data and structure analysis combined reveal interplay of structural rigidity and flexibility on selectivity of cysteine cathepsins.
Commun Biol, 6:450-450, 2023

PubMed Abstract: Addressing the elusive specificity of cysteine cathepsins, which in contrast to caspases and trypsin-like proteases lack strict specificity determining P1 pocket, calls for innovative approaches. Proteomic analysis of cell lysates with human cathepsins K, V, B, L, S, and F identified 30,000 cleavage sites, which we analyzed by software platform SAPS-ESI (Statistical Approach to Peptidyl Substrate-Enzyme Specific Interactions). SAPS-ESI is used to generate clusters and training sets for support vector machine learning. Cleavage site predictions on the SARS-CoV-2 S protein, confirmed experimentally, expose the most probable first cut under physiological conditions and suggested furin-like behavior of cathepsins. Crystal structure analysis of representative peptides in complex with cathepsin V reveals rigid and flexible sites consistent with analysis of proteomics data by SAPS-ESI that correspond to positions with heterogeneous and homogeneous distribution of residues. Thereby support for design of selective cleavable linkers of drug conjugates and drug discovery studies is provided.

PubMed: 37095140
DOI: 10.1038/s42003-023-04772-8

実験手法

X-RAY DIFFRACTION (1.75 Å)