Binding and Selectivity

It must be noted that the molecular dynamics simulations of acetylcholinesterase mentioned above are far too short to sample transitions over barriers that separate many conformational substates of the protein. But, for acetylcholinesterase similar behavior is observed for the two subunits of the 

What are the possible functional implications of such gating motions Ensuring the maximum possible speed of binding is clearly one function. For example, it is necessary to create a special environment around a substrate for enzymatic catalysis, but evolutionary pressure has forced the creation of this environment to happen very rapidly for certain enzymes. 

Although the above discussion focused on the binding of small molecules to biopolymers, similar issues arise in connection with the binding of biopolymers to one another. In particular, rapid motion (times of a few nanoseconds) of surface loops of proteins may facilitate the assembly of chaperonins [16] and allow the binding of multiple receptors in the case of certain fibronectin domains [4]. 

Recent studies have shown that conformational fluctuations of proteins can be important in structure-based drug discovery as in the discovery of an unexpected cryptic binding site in the HIV integrase enzyme during the course of molecular dynamics studies (Fig. 11.1) [24]. This helped to pave the way for the discovery of the first in a new class of antiviral agents for HIV/AIDS, the compound Isentress (raltegravir), which was licensed by the U.S. Food and Drug Administration in October 2007. A recent review of work in this area has been published by Amaro et al. [2]. 

Because only small displacements are required to open the gates in some of the systems mentioned above, biopolymer motion on short timescales (picoseconds to nanoseconds) can influence function. In other cases, larger displacements and longer timescales are important, as discussed in later sections. 

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Jensen, A. A., Sheppard, P. O., O Hara, P. J., Krogsgaard-Larsen, P and Brauner-Osbome, H. (2000) The role of Arg78 in the metabotropic glutamate receptor mGlui for agonist binding and selectivity. Eur. J. Pharmacol. 397, 247-253. 

Klymenko T, Papp B, Fischle W, Kocher T, Schelder M, Fritsch C, Wild B, Wilm M, Muller J (2006) A Polycomb group protein complex with sequence-specific DNA-binding and selective methyl-lysinebinding activities. Genes Dev 20 1110-1122... 

Chelating polymers must be developed and evaluated according to the type of waste being treated. Because some contaminants may be present in relatively low concentrations with respect to other ions in waste solutions, polymers that have high binding and selectivity for the particular contaminant must be developed. 

Scrimin. P.. Tecilla. P.. Tonellato, U. and Vignana. M. (1991) A water-soluble tweezers-like metalloreceptor Binding and selective catalytic properties. J. Chem. Soc., Chem. Commun.. 449. 

Although most polymerases conform to the general kinetic scheme, some polymerases have different mechanisms with regard to p/t binding and selection. Other aspects in the polymerase cycle such as dNTP binding, chemistry, and the conformational change will be discussed in later sections. 

Liu B. and Krieger M. (2002) Highly purified scavenger receptor class B, type I reconstituted into phosphatidylcholine/cholesterol liposomes mediates high affinity high density lipoprotein binding and selective lipid uptake. J. Biol. Chem. 277, 34125-34135. 

Zinc fingers are protein DNA-binding motifs have a finger stmcture, which is held together by Zn chelated by four cysteine S-donors. The binding and selectivity of Zn in proteins has been the subject of a short review. ... 

Roussel A, et al. Complexation of two proteic insect inhibitors to the active site of chymotrypsin suggests decoupled roles for binding and selectivity. J. Biol. Chem. 2001 276 38893-38898. 

We have used apoenzymes as molecular-recognition transporters for binding and selective transportation of molecules without production of unwanted chemical reactions on reactants. Figure 24.10 shows the design of membrane consisting of microporous polymer membrane sandwiched between two thin films of polypyrrole [3]. The apoenzymes are physically trapped within the pores of the membrane and polypyrrole films. More details regarding the fabrication of the membranes, materials, and experimental setup can be found in the Ref. [3]. 

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