Proteins ligand-induced conformational

Van Aalten, D.M.F., Findlay, J.B.C., Amadei, A., Berendsen,H.J.C. Essential dynamics of the cellular retinol-binding protein. Evidence for ligand-induced conformational changes. Protein Engin. 8 (1995) 1129-1136. 

The elegant genetic studies by the group of Charles Yanofsky at Stanford University, conducted before the crystal structure was known, confirm this mechanism. The side chain of Ala 77, which is in the loop region of the helix-turn-helix motif, faces the cavity where tryptophan binds. When this side chain is replaced by the bulkier side chain of Val, the mutant repressor does not require tryptophan to be able to bind specifically to the operator DNA. The presence of a bulkier valine side chain at position 77 maintains the heads in an active conformation even in the absence of bound tryptophan. The crystal structure of this mutant repressor, in the absence of tryptophan, is basically the same as that of the wild-type repressor with tryptophan. This is an excellent example of how ligand-induced conformational changes can be mimicked by amino acid substitutions in the protein. 

We have completed several structures each of NPl, NP2, and NP4 (31, 46 9, 110). These structures reveal the Rhodnius nitrophorins to have a fold dominated by an eight-stranded antiparallel beta-barrel, as shown in Fig. 15, and to rely on a remarkable ligand-induced conformational change for NO transport, described later. The structures confirm that the nitrophorins are completely unrelated to the globins, the only other heme-based gas transport proteins whose structures are known. Rather, their fold places them in the lipocalin family, for which several other examples are known (111-113). Our initial nitrophorin structure was of NPl and was determined using standard MIR and... 

Ligand-induced conformational changes in the protein can result in both cooperative and antagonistic binding effects on other ligands binding to the same protein. An example of a cooperative interaction is the enhancement of the interactions of progesterone and testosterone with human serum albumin (HSA) by the palmitate ion. 

Schuck, P., Taraporewala, Z., McPhie, P., and Patton, J. T. (2001). Rotavirus nonstructural protein NSP2 self-assembles into octamers that undergo ligand-induced conformational changes. / Biol. Chem. 276, 9679-9687. 

The collected Pocketome core provides a fairly comprehensive representation of transient protein-ligand interactions in PDB and allows characterization of the protein and induced conformational changes. Given a family of complexes formed by a particular protein domain, we compared each complex with all other complexes of the same composition, complexes of other compositions, and unbound structures. The unbound structures were also compared to one another to assess the degree of changes stemming from natural protein flexibility rather than induced by binding partners. 

Mizoue LS, Chazin W], Engineering and design of ligand-induced conformational change in proteins. Curr Opin Struct Biol 2002 12(4) 459-63. 

Cuneo MJ, Beese LS, Hellinga HW (2008) Ligand-induced conformational changes in a thermophilic ribose-binding protein. BMC Struct Biol 8 50... 

However, despite these difficulties it should be possible to apply a modified version of Eq. (6) to ligand-induced conformational change in proteins for comparative purposes, i.e. by deriving AGb for related ligands under identical experimental conditions and at a temperature as close to physiological as possible. The kcat form of... 

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