Publication
Title
Study of the structural and dynamic effects in the FimH adhesin upon alpha-D-Heptyl mannose binding
Author
Abstract
Uropathogenic Escherichia coli cause urinary tract infections by adhering to mannosylated receptors on the human urothelium via the carbohydrate-binding domain of the FimH adhesin (FimH(L)). Numerous alpha-D-mannopyranosides, including alpha-D-heptyl mannose (HM), inhibit this process by interacting with FimH(L). To establish the molecular basis of the high-affinity HM binding, we solved the solution structure of the apo form and the crystal structure of the FimH(L)-HM complex. NMR relaxation analysis revealed that protein dynamics were not affected by the sugar binding, yet HM addition promoted protein dimerization, which was further confirmed by small-angle X-ray scattering. Finally, to address the role of Y48, part of the "tyrosine gate" believed to govern the affinity and specificity of mannoside binding, we characterized the FimH(L) Y48A mutant, whose conformational, dynamical, and HM binding properties were found to be very similar to those of the wild-type protein.
Language
English
Source (journal)
Journal of medicinal chemistry. - Washington, D.C., 1963, currens
Publication
Washington, D.C. : 2014
ISSN
0022-2623 [print]
1520-4804 [online]
Volume/pages
57 :4 (2014) , p. 1416-1427
ISI
000332187700021
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Publication type
Subject
External links
Web of Science
Record
Identification
Creation 04.10.2018
Last edited 04.09.2021