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Carnosic Acid: A Novel Selective Inhibitor of ERAP1 by Direct Binding and Its Modulation of Antigen Processing and Presentation.
Wu, Jiaqi; Li, Zhao; Liu, Xiaofan; Feng, Dongyan; Liang, Ruichao; Su, Xin; Li, Dahong; Hua, Huiming; Cao, Hao.
Afiliación
  • Wu J; School of Life Science and Biopharmaceutics and Key Laboratory of Microbial Pharmaceutics, Liaoning Province, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, P. R. China.
  • Li Z; Central Laboratory, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210000, P. R. China.
  • Liu X; School of Life Science and Biopharmaceutics and Key Laboratory of Microbial Pharmaceutics, Liaoning Province, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, P. R. China.
  • Feng D; Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, and School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, P. R. China.
  • Liang R; School of Life Science and Biopharmaceutics and Key Laboratory of Microbial Pharmaceutics, Liaoning Province, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, P. R. China.
  • Su X; School of Life Science and Biopharmaceutics and Key Laboratory of Microbial Pharmaceutics, Liaoning Province, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, P. R. China.
  • Li D; Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, and School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, P. R. China.
  • Hua H; Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, and School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, P. R. China.
  • Cao H; School of Life Science and Biopharmaceutics and Key Laboratory of Microbial Pharmaceutics, Liaoning Province, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, P. R. China.
J Agric Food Chem ; 72(31): 17343-17355, 2024 Aug 07.
Article en En | MEDLINE | ID: mdl-39024058
ABSTRACT
ERAP1 is an emerging target for a large subclass of severe autoimmune diseases known as "MHC-I-opathy", together with tumor immunity. Nevertheless, effective inhibitors targeting ERAP1 remain a challenge. In this study, a novel food-derived natural product ERAP1-targeting inhibitor, carnosic acid, was identified, and to our knowledge, it is one of the best active compounds among the highly selective inhibitors targeting the orthosteric site of ERAP1. The results reveal that carnosic acid could bind strongly, like a key to the ERAP1 active site in the biased S1' pocket, which is different from the binding mode of the existing orthosteric site inhibitors. HLA-B27-mediated cell modeling validated that carnosic acid has the activity to reverse the AS-associated cellular phenotype brought on by ERAP1 through inhibition. Our findings provide insights into the design of potent inhibitors against the ERAP1 orthosteric site and the discovery of a key direct target of carnosic acid.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antígenos de Histocompatibilidad Menor / Presentación de Antígeno / Abietanos / Aminopeptidasas Límite: Humans Idioma: En Revista: J Agric Food Chem Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antígenos de Histocompatibilidad Menor / Presentación de Antígeno / Abietanos / Aminopeptidasas Límite: Humans Idioma: En Revista: J Agric Food Chem Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos