Clamshell dynamically accommodating

Nevertheless, the wealth of structural data permits a structural classification of SBPs, wherein the hinge region is the most defining feature of each sub-group or cluster (Figure 1) (Berntsson et al., 2010; Scheepers et al., 2016).Crystal structures of the same protein, but with different ligands bound, generally report the same degree of closing of the SBP (Trakhanov et al., 2005; Nishitani et al., 2012; Pandey et al., 2016; Magnusson et al., 2004; Quiocho et al., 1997).

Recent advances in single-molecule methodologies now permit new insight into the conformational heterogeneity, dynamics and occurrences of rare events in SBPs (Feng et al., 2016; Gouridis et al., 2015; Kim et al., 2013; Seo et al., 2014; Husada et al., 2015; Lerner et al., 2018), which are difficult to obtain in bulk measurements.

Such observations question the precise relationship between SBP-ligand interactions, SBP conformational changes and their involvement in transport function.

A range of biophysical and structural approaches have been used to decipher the mechanistic basis of SBP-ligand interactions (Shilton et al., 1996; Quiocho and Ledvina, 1996; Trakhanov et al., 2005; Hall et al., 1997b; Skrynnikov et al., 2000).

Additional complexity exists for the coupling of SBP conformational switching and the ligand recognition process, as crystallographic (Flocco and Mowbray, 1994; Oswald et al., 2008), nuclear magnetic resonance (NMR) (Tang et al., 2007) and single-molecule (Feng et al., 2016; Gouridis et al., 2015) studies indicate that SBPs can undergo intrinsic conformational changes in the absence of substrate.

Furthermore, crystal structures of the SBPs Mal E and a D-xylose SBP were obtained in an open ligand-bound conformation (Duan and Quiocho, 2002; Sooriyaarachchi et al., 2010).

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