Selective molecular Basis

Doyle, D.A., et al. The structure of the potassium channel molecular basis of K+ conduction and selectivity. Science 280 69-77, 1998. 

Dutzler R, Campbell EB, Cadene M et al (2002) X-ray structure of the C1C chloride channel at 3.0 A resolution molecular basis of anion selectivity. Nature 415 287—294... 

This chapter briefly reviews the present understanding of the chemistry, origin, and distribution of the saxitoxins and methods for their detection. The second section of this chapter discusses studies on their pharmacology directed toward an understanding of the molecular basis for their strong, highly selective interaction with the sodium channel binding site. 

Under basal conditions, PKC is predominantly a cytoplasmic protein. Upon activation by Ca2+ or DAG, the enzyme associates with the plasma membrane, the site of many of its known physiological substrates, including receptors and ion channels. In fact, the translocation of PKC from the cytoplasm to the membrane has long been used as an experimental measure of enzyme activation. Such translocation has often been assayed by phorbol ester binding phorbol esters are tumor-promoting agents that selectively bind to and activate PKC. The molecular basis of the translocation of PKC from the cytoplasm to the plasma membrane has been solved. Subsequent to activation, PKC binds with high affinity to a series of membrane-associated proteins, termed receptors for... 

In neurons and non-neuronal cells, kinesin is associated with a variety of MBOs, ranging from synaptic vesicles to mitochondria to lysosomes. In addition to its role in fast axonal transport and related phenomena in non-neuronal cells, kinesin appears to be involved in constitutive cycling of membranes between the Golgi and endoplasmic reticulum. However, kinesin is not associated with all cellular membranes. For example, the nucleus, membranes of the Golgi complex and the plasma membrane all appear to lack kinesin. Kinesin interactions with membranes are thought to involve the light chains and carboxyl termini of heavy chains. However, neither this selectivity nor the molecular basis for binding of kinesin and other motors to membranes is well understood. 

Wess, J. (1998) Molecular basis of receptor/G protein-coupling selectivity. Pharmacol. Then 80, 231-264. 

Benz, R., Schmid, A., van der Ley, P. and Tommassen, J. (1989). Molecular basis of porin selectivity membrane experiments with OmpC-PhoE and OmpF-PhoE hybrid proteins of Escherichia coli K-12, Biochim. Biophys. Acta, 981, 8-14. 

The most difficult problem we face in deciding to use a basis of hybrids which reflects the molecular symmetry is how do we choose such a basis in view of the enormous numerical difficulties involved in optimising the non-linear parameters in molecular calculations The real question is are there any rules for this choice, can the optimisation be done (at least approximately) once and for all The chemical evidence is for us — it is the most basic concept of the theory of valence that particular electronic sub-structures tend to be largely environment-independent. How can we select our basis to reflect this chemical fact ... 

Recapitulating the foregoing discussion, it is clearly not our opinion that solution experiments appear to be inadequate for the purpose of comparison with molecular theories. However, we want to point out that due to the evident shortcomings of present theoretical and computational facilities a distinct scepticism is necessary in order to avoid the production of meaningless data. Of course, the solution experiments remain the main source of information, the data of which must be explained by theory. At the present stage of knowledge it is only possible to pick out selected properties of solutions which can be described satisfactorily on a molecular basis. For instance, referring to Frank and Wen s model of solvation shells W, the structure of the inner shell should not be modified too much by... 

R., and Crews, C. M. Crystal structure of epoxomidn 20S proteasome reveals a molecular basis for selectivity of alpha, beta -epoxyketone proteasome inhibitors. J. Am. Chem. Soc. 2000b, 122, 1237-1238. 

Poux, A.N. and Marmorstein, R. (2003) Molecular basis for Gcn5/PCAE histone acetyltransferase selectivity for histone and nonhistone substrates. Biochemistry, 42 (49), 14366-14374. 

The use of tailor made additives holds great promise in the area of crystal growth and morphology control. The routine selection and use of these type of additives will require a fundamental understanding of the mechanism which the additives work on a molecular basis. At the same time, the effect of solvent molecules on the crystal growth process is another related and important problem. In both instances, the relationship between internal aystal structure, aystal growth rate, solvent and impurities are needed to predict the habit of a crystal and thus allow seleaion of the proper conditions and components required to obtain a desired habit... 

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