Insights into substrate binding and catalysis in bacterial type I dehydroquinase
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|Title:||Insights into substrate binding and catalysis in bacterial type I dehydroquinase
|Author:||Maneiro Rey, María
Peón López, Antonio
Lence Quintana, Emilio José
Otero, José M.
Van Raaij, Mark J.
Hawkins, Alastair R.
González Bello, Concepción
|Affiliation:||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
|Subject:||Dehydroquinase | Enzymatic mechanism | MD simulation | Salmonella typhi | X-ray crystallography ||
|Date of Issue:||2014-09-15
|Citation:||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
|Abstract:||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|
|Rights:||© 2014 Biochemical Society