5CGB

Crystal structure of FimH in complex with heptyl alpha-D-septanoside

Summary for 5CGB

• Entry DOI: 10.2210/pdb5cgb/pdb
• Descriptor: Protein FimH, (6R)-1,6-anhydro-2-O-heptyl-6-(hydroxymethyl)-D-galactitol, SULFATE ION, ... (4 entities in total)
• Functional Keywords: uti, lectin, urinary tract infection, type 1 fimbriae, pilus, inhibitor, sugar binding protein
• Biological source: Escherichia coli K-12
• Cellular location: Fimbrium: P08191
• Total number of polymer chains: 2
• Total formula weight: 34610.52

Authors

Jakob, R.P.,Preston, R.P.,Zihlmann, P.,Fiege, B.,Sager, C.P.,Vannam, R.,Rabbani, S.,Zalewski, A.,Maier, T.,Ernst, B.,Peczuh, M. (deposition date: 2015-07-09, release date: 2016-07-20, Last modification date: 2024-11-13)

Primary citation

Sager, C.P.,Fiege, B.,Zihlmann, P.,Vannam, R.,Rabbani, S.,Jakob, R.P.,Preston, R.C.,Zalewski, A.,Maier, T.,Peczuh, M.W.,Ernst, B.
The price of flexibility - a case study on septanoses as pyranose mimetics.
Chem Sci, 9:646-654, 2018

PubMed Abstract: Seven-membered ring mimetics of mannose were studied as ligands for the mannose-specific bacterial lectin FimH, which plays an essential role in the first step of urinary tract infections (UTI). A competitive binding assay and isothermal titration calorimetry (ITC) experiments indicated an approximately ten-fold lower affinity for the seven-membered ring mannose mimetic 2--heptyl-1,6-anhydro-d--d-galactitol () compared to -heptyl α-d-mannopyranoside (), resulting exclusively from a loss of conformational entropy. Investigations by solution NMR, X-ray crystallography, and molecular modeling revealed that establishes a superimposable H-bond network compared to mannoside , but at the price of a high entropic penalty due to the loss of its pronounced conformational flexibility. These results underscore the importance of having access to the complete thermodynamic profile of a molecular interaction to "rescue" ligands from entropic penalties with an otherwise perfect fit to the protein binding site.

PubMed: 29629131
DOI: 10.1039/c7sc04289b

Experimental method

X-RAY DIFFRACTION (1.6 Å)