Cooperative binding sites

Viles, J. H., Cohen, F. E., Prusiner, S. B., Goodin, D. B., Wright, P. E., and Dyson, H. J. (1999). Copper binding to the prion protein Structural implications of four identical cooperative binding sites. Proc. Natl. Acad. Sci. USA 96, 2042-2047. 

Hartwig U, Gerlach D, Fleischer B Major histocompatibility complex class II binding site for streptococcal pyrogenic (erythrogenic) toxin A. Med Microbiol Immunol 1994 183 257-264. Hudson KR, Tiedemann RE, Urban RG, Lowe SC, Strominger JL, Fraser JD Staphylococcal enterotoxin A has two cooperative binding sites on major histocompatibility complex class II. J Exp Med 1995 182 711-720. 

The basic kinetic properties of this allosteric enzyme are clearly explained by combining Monod s theory and these structural results. The tetrameric enzyme exists in equilibrium between a catalytically active R state and an inactive T state. There is a difference in the tertiary structure of the subunits in these two states, which is closely linked to a difference in the quaternary structure of the molecule. The substrate F6P binds preferentially to the R state, thereby shifting the equilibrium to that state. Since the mechanism is concerted, binding of one F6P to the first subunit provides an additional three subunits in the R state, hence the cooperativity of F6P binding and catalysis. ATP binds to both states, so there is no shift in the equilibrium and hence there is no cooperativity of ATP binding. The inhibitor PEP preferentially binds to the effector binding site of molecules in the T state and as a result the equilibrium is shifted to the inactive state. By contrast the activator ADP preferentially binds to the effector site of molecules in the R state and as a result shifts the equilibrium to the R state with its four available, catalytically competent, active sites per molecule. 

Kroeger, P.E., Morimoto, R.L (1994). Selection of new HSFI and HSF2 DNA-binding sites reveals difference in trimer cooperativity. Mol. Cell. Biol. 14, 7592-7603. ... 

Fig. 3.6 Polyamide-DNA binding motifs targeting longer DNA sequences. Overlapped and slipped homodimers depending on the sequence context, six-ring polyamides with central p-Ma residues can bind to DNA as fully overlapped homodimers, recognizing 11 bp, or as slipped homodimers, recognizing 13 bp. Extended hairpin extended conformation increases binding site size (to 9 bp) and enhances binding affinity. Cooperative dimer a cooperatively binding hairpin polyamide can...

A linear form of the Hill equation is used to evaluate the cooperative substrate-binding kinetics exhibited by some multimeric enzymes. The slope n, the Hill coefficient, reflects the number, nature, and strength of the interactions of the substrate-binding sites. A... 

Proteins with the helix-turn-helix or leucine zipper motifs form symmetric dimers, and their respective DNA binding sites are symmetric palindromes. In proteins with the zinc finger motif, the binding site is repeated two to nine times. These features allow for cooperative interactions between binding sites and enhance the degree and affinity of binding. 

The Ca binding sites of the enzyme remained functional after DEPC treatment [368], but the cooperativity of Ca binding seen in native Ca -ATPase was abolished. The Ca " binding to the DEPC-modified Ca " -ATPase could be described in terms of two independent Ca binding sites with Xca of 14 uM and 0.5 (iM, respectively. The phosphorylation of DEPC-modified Ca -ATPase followed closely the saturation of the site with the higher Ca affinity [368]. 

Self-assembled structures can be closed if all the potential binding sites are utilized, or open if they are not. Closed assemblies have a definite geometry and stoichiometry, while open assemblies exist as mixtures of oligomers or polymers of varying stoichiometry. In addition, the self-assembled structure can be classified as cooperative if the multiple binding interactions reinforce each other to yield enhanced stability, or trivial if the binding interactions do not cooperate in the... 

The simplest model that can describe allosteric interactions at GPCRs is the ternary complex allosteric model [9], As shown in Figure 1, according to this model two parameters define the actions of allosteric agent (X) its affinity for the unoccupied receptor (Kx) and its cooperativity (a) with the ligand (A) that interacts at the primary binding site a < 1 represents negative cooperativity a = 1, no cooperativity a > 1, positive cooperativity. 

---