46 resultados para Hepatic Enzymes
Filtro por publicador
- ABACUS. Repositorio de Producción Científica - Universidad Europea (2)
- Aberdeen University (5)
- Abertay Research Collections - Abertay University’s repository (2)
- Academic Archive On-line (Stockholm University; Sweden) (1)
- Acceda, el repositorio institucional de la Universidad de Las Palmas de Gran Canaria. España (1)
- AMS Tesi di Dottorato - Alm@DL - Università di Bologna (3)
- Aquatic Commons (9)
- ARCA - Repositório Institucional da FIOCRUZ (1)
- ArchiMeD - Elektronische Publikationen der Universität Mainz - Alemanha (2)
- Archimer: Archive de l'Institut francais de recherche pour l'exploitation de la mer (1)
- Archive of European Integration (2)
- Archivo Digital para la Docencia y la Investigación - Repositorio Institucional de la Universidad del País Vasco (5)
- Aston University Research Archive (11)
- Biblioteca Digital da Produção Intelectual da Universidade de São Paulo (29)
- Biblioteca Digital da Produção Intelectual da Universidade de São Paulo (BDPI/USP) (15)
- Biblioteca Digital de Teses e Dissertações Eletrônicas da UERJ (3)
- Bioline International (1)
- BORIS: Bern Open Repository and Information System - Berna - Suiça (133)
- Brock University, Canada (6)
- CaltechTHESIS (2)
- Cambridge University Engineering Department Publications Database (1)
- CentAUR: Central Archive University of Reading - UK (34)
- Chinese Academy of Sciences Institutional Repositories Grid Portal (41)
- Cochin University of Science & Technology (CUSAT), India (23)
- CORA - Cork Open Research Archive - University College Cork - Ireland (2)
- Deakin Research Online - Australia (36)
- Digital Commons at Florida International University (1)
- DigitalCommons@The Texas Medical Center (19)
- DRUM (Digital Repository at the University of Maryland) (1)
- Duke University (4)
- Glasgow Theses Service (1)
- Helda - Digital Repository of University of Helsinki (25)
- Illinois Digital Environment for Access to Learning and Scholarship Repository (1)
- Indian Institute of Science - Bangalore - Índia (56)
- Memorial University Research Repository (1)
- National Center for Biotechnology Information - NCBI (82)
- Nottingham eTheses (2)
- Plymouth Marine Science Electronic Archive (PlyMSEA) (13)
- Publishing Network for Geoscientific & Environmental Data (20)
- QSpace: Queen's University - Canada (2)
- QUB Research Portal - Research Directory and Institutional Repository for Queen's University Belfast (46)
- Queensland University of Technology - ePrints Archive (21)
- Repositório Alice (Acesso Livre à Informação Científica da Embrapa / Repository Open Access to Scientific Information from Embrapa) (1)
- Repositório Científico da Universidade de Évora - Portugal (1)
- Repositório Digital da UNIVERSIDADE DA MADEIRA - Portugal (1)
- Repositório Institucional da Universidade de Aveiro - Portugal (1)
- Repositório Institucional da Universidade Federal de São Paulo - UNIFESP (1)
- Repositório Institucional da Universidade Federal do Rio Grande do Norte (1)
- Repositorio Institucional de la Universidad de Málaga (1)
- Repositório Institucional dos Hospitais da Universidade Coimbra (1)
- Repositório Institucional UNESP - Universidade Estadual Paulista "Julio de Mesquita Filho" (163)
- RUN (Repositório da Universidade Nova de Lisboa) - FCT (Faculdade de Cienecias e Technologia), Universidade Nova de Lisboa (UNL), Portugal (3)
- SAPIENTIA - Universidade do Algarve - Portugal (2)
- Savoirs UdeS : plateforme de diffusion de la production intellectuelle de l’Université de Sherbrooke - Canada (1)
- Scielo España (1)
- Scientific Open-access Literature Archive and Repository (2)
- Universidad de Alicante (2)
- Universidad del Rosario, Colombia (3)
- Universidad Politécnica de Madrid (3)
- Universidade Complutense de Madrid (1)
- Universidade de Lisboa - Repositório Aberto (2)
- Universidade Federal do Pará (6)
- Universidade Federal do Rio Grande do Norte (UFRN) (6)
- Universidade Técnica de Lisboa (1)
- Universitat de Girona, Spain (1)
- Université de Lausanne, Switzerland (8)
- Université de Montréal (3)
- Université de Montréal, Canada (24)
- Université Laval Mémoires et thèses électroniques (2)
- University of Connecticut - USA (1)
- University of Michigan (7)
- University of Queensland eSpace - Australia (64)
- University of Washington (1)
- WestminsterResearch - UK (3)
- Worcester Research and Publications - Worcester Research and Publications - UK (1)
Resumo:
Mevalonate pathway is of important clinical, pharmaceutical and biotechnological relevance. However, lack of the understanding of the phosphorylation mechanism of the kinases in this pathway has limited rationally engineering the kinases in industry. Here the phosphorylation reaction mechanism of a representative kinase in the mevalonate pathway, phosphomevalonate kinase, was studied by using molecular dynamics and hybrid QM/MM methods. We find that a conserved residue (Ser106) is reorientated to anchor ATP via a stable H-bond interaction. In addition, Ser213 located on the α-helix at the catalytic site is repositioned to further approach the substrate, facilitating the proton transfer during the phosphorylation. Furthermore, we elucidate that Lys101 functions to neutralize the negative charge developed at the β-, γ-bridging oxygen atom of ATP during phosphoryl transfer. We demonstrate that the dissociative catalytic reaction occurs via a direct phosphorylation pathway. This is the first study on the phosphorylation mechanism of a mevalonate pathway kinase. The elucidation of the catalytic mechanism not only sheds light on the common catalytic mechanism of GHMP kinase superfamily, but also provides the structural basis for engineering the mevalonate pathway kinases to further exploit their applications in the production of a wide range of fine chemicals such as biofuels or pharmaceuticals.