The Molecular Mechanism of Substrate Recognition and Catalysis of the Membrane Acyltransferase PatA from Mycobacteria
| Autor: | Montse Tersa, David Albesa-Jové, Martine Gilleron, Beatriz Trastoy, Marcelo E. Guerin, Carme Rovira, Lluís Raich, Jacques Prandi |
|---|---|
| Přispěvatelé: | Departament de Quimica Fisica and Institut de Quimica Teorica i Computacional (IQTCUB), Universitat de Barcelona (UB), Departamento de Bioquimica, Universidad del Pais Vasco / Euskal Herriko Unibertsitatea [Espagne] (UPV/EHU), Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Colorado State University [Fort Collins] (CSU) |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Models Molecular Mannosides Protein Conformation Mycobacterium smegmatis Mannose Crystallography X-Ray Biochemistry Catalysis 03 medical and health sciences chemistry.chemical_compound Protein structure Biosynthesis Bacterial Proteins Moiety Binding site ComputingMilieux_MISCELLANEOUS Binding Sites biology Active site General Medicine Recombinant Proteins 3. Good health [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biophysics 030104 developmental biology chemistry Acyltransferase biology.protein Molecular Medicine lipids (amino acids peptides and proteins) Acyltransferases |
| Zdroj: | ACS Chemical Biology ACS Chemical Biology, American Chemical Society, 2017, 13 (1), pp.131-140. ⟨10.1021/acschembio.7b00578⟩ |
| ISSN: | 1554-8937 1554-8929 |
| DOI: | 10.1021/acschembio.7b00578⟩ |
| Popis: | Glycolipids play a central role in a variety of important biological processes in all living organisms. PatA is a membrane acyltransferase involved in the biosynthesis of phosphatidyl-myo-inositol mannosides (PIMs), key structural elements, and virulence factors of Mycobacterium tuberculosis. PatA catalyzes the transfer of a palmitoyl moiety from palmitoyl-CoA to the 6-position of the mannose ring linked to the 2-position of inositol in PIM1/PIM2. We report here the crystal structure of PatA in the presence of 6-O-palmitoyl-α-d-mannopyranoside, unraveling the acceptor binding mechanism. The acceptor mannose ring localizes in a cavity at the end of a surface-exposed long groove where the active site is located, whereas the palmitate moiety accommodates into a hydrophobic pocket deeply buried in the α/β core of the protein. Both fatty acyl chains of the PIM2 acceptor are essential for the reaction to take place, highlighting their critical role in the generation of a competent active site. By the use of com... |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|