دورية أكاديمية
Insights into substrate binding and catalysis in bacterial type I dehydroquinase
| العنوان: | Insights into substrate binding and catalysis in bacterial type I dehydroquinase |
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| المؤلفون: | Maneiro Rey, María, Peón López, Antonio, Lence Quintana, Emilio José, Otero Casas, José Manuel, Raaij, Mark J. van, Thompson, Paul, Hawkins, Alastair R., González Bello, Concepción |
| المساهمون: | Universidade de Santiago de Compostela. Centro de Investigación en Química Biolóxica e Materiais Moleculares, Universidade de Santiago de Compostela. Departamento de Bioquímica e Bioloxía Molecular, Universidade de Santiago de Compostela. Departamento de Química Orgánica |
| بيانات النشر: | Portland Press |
| المجموعة: | Minerva - Repositorio institucional da Universidade de Santiago de Compostela (USC) |
| مصطلحات موضوعية: | Dehydroquinase, Enzymatic mechanism, MD simulation, Salmonella typhi, X-ray crystallography |
| الوصف: | Structural, biochemical and computational studies to study substrate binding and the role of the conserved residues of the DHQ1 (type I dehydroquinase) enzyme active site are reported in the present paper. The crystal structure of DHQ1 from Salmonella typhi in complex with (2R)-2-methyl-3-dehydroquinic acid, a substrate analogue, was solved at 1.5 Å. The present study reveals a previously unknown key role for conserved Glu, Phe and Met and Gln, Pro and Ala residues, with the latter three being located in the flexible substrate-covering loop. Glu was shown to be responsible for the folding of this loop and for the dramatic reduction of its flexibility, which triggers active site closure. Glu46 was found to be key in bringing the substrate close to the lysine/histidine catalytic pocket to initiate catalysis. The present study could be useful in the rational design of inhibitors of this challenging and recognized target for the development of novel herbicides and antimicrobial agents ; This work was supported by the Spanish Ministry of Science and Innovation (grant number SAF2010-15076) and via FPU fellowships to M.M. and A.P., the Xunta de Galicia (grant number GRC2013/041) and via postdoctoral fellowships to E.L. and J.M.O., and by the European Regional Development Fund (ERDF) ; SI |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0264-6021 1470-8728 |
| العلاقة: | https://doi.org/10.1042/BJ20140614Test; info:eu-repo/grantAgreement/MICINN/Plan Nacional de I+D+i 2008-2011/SAF2010-15076/ES/ANTIBIOTICOS INHIBIDORES DE NOVEDOSAS DIANAS TERAPEUTICAS: DISEÑO, SINTESIS Y EVALUACION BIOLOGICA; Maneiro, M., Peón, A., Lence, E., Otero, J., Van Raaij, M., & Thompson, P. et al. (2014). Insights into substrate binding and catalysis in bacterial type I dehydroquinase. Biochemical Journal, 462(3), 415-424. doi:10.1042/bj20140614; http://hdl.handle.net/10347/16943Test |
| DOI: | 10.1042/BJ20140614 |
| الإتاحة: | https://doi.org/10.1042/BJ20140614Test http://hdl.handle.net/10347/16943Test |
| حقوق: | © 2014 Biochemical Society ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.BA582859 |
| قاعدة البيانات: | BASE |
| تدمد: | 02646021 14708728 |
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| DOI: | 10.1042/BJ20140614 |