Anti conformer binding

Different conformations of acetylchohne bind different receptors. The gauche conformation binds the muscarinic receptor of postganglionic parasympathetic nerves the anti conformation binds nicotinic receptors at ganglia and the acetylcholine receptor at neuromuscular junctions. 

The anti conformation preferred by the adenine residue in 5 -AMP (Figure lb) disposes this nucleotide to simultaneous inner-sphere binding of metal ions both to the phosphate oxygen and N-7 atoms. As would be expected, neither 2 -nor 3 -AMP (Figure Ic) is able to participate in forming the same type of complex for steric reasons. As was shown in experiments involving Mg +, Mn +, Cd +, Co +, and Cu +,... 

Anti-inducers bind to the conformation of repressors, such as the lac repressor, that are capable of binding DNA. They occupy a site that overlaps that for the inducer and, therefore, compete for binding to the repressor. 

Positive ion fast atom bombardment mass spectrometry has been used to develop a procedure for the identification of cyclic nucleotides. Computational studies have shovm that cGMP is expected to prefer the syn-conformation, whilst cAMP prefers the anti-conformation.An intramolecular hydrogen bond between the C-2 amine fvmction of guanine and the axial oxygen atom of the cyclic phosphate is implicated in increasing the relative stability of the syn-conformation of cOlP. These conformational profiles may help to explain selectivity of binding and activation of proteins by cyclic nucleotides. 

Aromatic diimides 71 and 72 derived from 9-epi-9-amino cinchona alkaloids and pyromellitic or 1,4,5,8-naphthalenetetracarboxylic anhydride have been designed by Gawronski and Kacprzak as novel chiral receptors. These triads are present at room temperature as equimolar mixture of syn and anti conformers, resulting from restricted rotation around the imide C—N bonds. These triads show high affinity toward carboxylic adds. The syn conformer binds preferentially 1,2-dicarboxylates in a 1 1 molecular ratio whereas the anti conformer is selective toward monocarbox-ylates forming a complex in a ratio 1 2 (triad acid). The response is sensitive and could be observed by either 1H NMR or by CD spectroscopy even when equimolar amounts of the adds are present in the solution. The competition experiments have shown a higher selectivity of triads toward 1,2-dicarboxylates [140],... 

Reaction specificity appears to correlate with the conformation of the bound NAD(P) about the C-N bond. There appear to be two minima in free solution, both apparently dictated by the need to have interactions between large substituents staggered, and hence the pyridine ring eclipsing the anomeric hydrogen, syn and anti. (Figure 6.61). X-ray studies of a range of enzymes in complex with coenzyme showed that B-side-specific enzymes bind the coenzyme in the syn conformation and A-side-specific enzymes bind in the anti conformation. 

Figure 17 Putative substrate-binding pocket of NtHCT in binary (a) and ternary (b) compiexes. The giycosidic bond dihedrai angies of the adenosine unit of p-coumaroyi CoA (9) in both binary and ternary compiexes adopt an anti conformation, in insets in the iower right corners of (a) and (b), the experimentai difference Fourier maps( Fo - Fo ) correspond top-coumaroyi CoA (9) and shikimic acid (29) in binary (a) and ternary compiexes (b) of NtHCT, respectiveiy, and are shown at a contour ievei of 2.5ct. The participating residues for binding and cataiytic reaction mechanism are shown in green (from domain 1), pink (from domain 2), and red ( HXXXD motif). The sait bridge and/or hydrogen bonds are represented by dotted iines. Water moiecuies are shown as red spheres.

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