3ZPD

Solution structure of the FimH adhesin carbohydrate-binding domain

Summary for 3ZPD

• Entry DOI: 10.2210/pdb3zpd/pdb
• NMR Information: BMRB: 19066
• Descriptor: FIMH (1 entity in total)
• Functional Keywords: cell adhesion, bacterial adhesin, urinary tract infection, carbohydrate
• Biological source: ESCHERICHIA COLI
• Total number of polymer chains: 1
• Total formula weight: 16916.83

Authors

van Nuland, N.A.J.,Vanwetswinkel, S.,Vranken, W.F.,Buts, L. (deposition date: 2013-02-27, release date: 2014-02-12, Last modification date: 2024-11-20)

Primary citation

Vanwetswinkel, S.,Volkov, A.N.,Sterckx, Y.G.J.,Garcia-Pino, A.,Buts, L.,Vranken, W.F.,Bouckaert, J.,Roy, R.,Wyns, L.,Van Nuland, N.A.J.
Study of the Structural and Dynamic Effects in the Fimh Adhesin Upon Alpha-D-Heptyl Mannose Binding.
J.Med.Chem., 57:1416-, 2014

PubMed 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 (FimHL). Numerous α-d-mannopyranosides, including α-d-heptyl mannose (HM), inhibit this process by interacting with FimHL. 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 FimHL-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 FimHL Y48A mutant, whose conformational, dynamical, and HM binding properties were found to be very similar to those of the wild-type protein.

PubMed: 24476493
DOI: 10.1021/JM401666C

Experimental method

SOLUTION NMR