Table 1.

Residues from the FimH lectin domain important for its function (and discussed in this review) are listed. These residues are either (i) involved in binding of the algycon moiety in the FimH mannose-binding pocket, (ii) important for the conformational change of FimH or (iii) have been shown to be involved in promising alternative binding positions. For each residue the available experimental evidence as well as the insight gained from molecular simulation shortly summarized. The most promising residues are highlight by an asterisk. The sequence from the UPEC strain UTI89 was used.

Residue	Important Due to	Exp. Evidence	Insight from Molecular Simulation
Ile13	Located in the clamp loop (changes conformation due to shear force) Possibly involved in alternative binding position	Ile13 forms van der Waals interactions with the C1–C2 bond of mannose [42] Crystal structures of the HA and LA state highlight the movement of the clamp loop [43]	The aglycon moiety of the C117 and of biantennary mannosides orients towards Ile13 [39,44].
Glu50	Part of a possible new binding site for anti-adhesives	EDTA binding site [38] Implied in the shear-force dependent conformational change [45] Less adhesion of the E50A mutant under shear [45]
Ile52	Belongs to the tyrosine gate	Attributed to the tyrosine gate on the basis of crystal structures [42]	Mediates coupled motion of Tyr48 and Tyr137 [38]
Thr53	Part of a possible new binding site for anti-adhesives	EDTA binding site [38] Implied in the shear-force dependent conformational change [45] Less adhesion of the T53A mutant under shear [45]
Asn136	Part of a possible new binding site for anti-adhesives	EDTA binding site [38]
Tyr137	Belongs to the tyrosine gate Binding of the aglycon part in the mannose-binding moiety	Y137A mutation significantly reduces FimH affinity towards f HM [38]	The flexibility of the bound HM is increased in the Y137A mutant; The apo mutant already is in a quasi-bound configuration [38]
Thr158	Implicated in the shear-force dependent conformational change	Natural variation leads to bacteria with different stress responses [22,46,47]	A force was applied to this residue in the sMD simulation [48]