Drug-binding sites

Fig. 15. Drug binding sites associated with the GABA receptor—channel complex where (— -) represents the carbon backbone of GABA agonists.

C. F., Mistry, P., Charlton, P., Caliaghan, R., Communication between multiple drug binding sites on P-glycoprotein, Mol. Pharmacol. 2000, 58, 624-632. 

Loo, T. W., Clarke, D. M., Vanadate trapping of nucleotide at the ATP-binding sites of human multidrug resistance P-glycoprotein exposes different residues to the drug-binding site, Proc. Natl. Acad. Sci. USA 2002, 99, 3511-3516. 

The evolving structural insights into the hERG drug-binding site show that this channel has a relatively larger inner cavity, with many aromatic and polar residues intricately positioned to interact with drugs. Utilization of in silico techniques, refined... 

Fernandez, D., Ghanta, A., Kauffman, G. W. and Sanguinetti, M.C. (2004) Physicochemical features of the hERG channel drug binding site. The Journal of Biological Chemistry, 279, 10120-10127. 

A clear understanding of drug-binding sites and the mechanisms of transport/ inhibition as well as the resolution of P-gp crystal structures in complex with different substrates/inhibitors will definitively aid in the development of better models. However, considering the complexity underlying these antitargets, we strongly believe that this will not be reached in the near future. 

Benkestock, K., Edlund, P. O., Roeraade, J. Electrospray ionization mass spectrometry as a tool for determination of drug binding sites to human serum albumin by noncovalent interaction. Rapid Commun Mass Spectrom 2005, 19, 1637-1643. 

Fig. 3. Possible interactions between PKC and MDRl-mediated drug resistance. Activation of PKC might activate the drug efflux by phosphorylation of PGP (A), induce or activate proteins which modulate PGP (B, Castro et al., 1999), or induce the transcription and translation of MDRl-mRNA (C). Inhibitors of PKC might prevent phosphorylation of PGP leading to a decrease the drug efflux (D). inhibit the efflux of drugs by direct interaction with the drug binding site(s) or the ATP-binding sites of PGP (E), or prevent the expression of MDRl-mRNA (F)...

Nayal M, Honig B (2006) On the nature of cavities on protein surfaces application to the identification of drug-binding sites. Proteins Struct Funct Bioinformatics 63 892-906... 

Drug distribution in elderly patients may be altered by hypoalbuminemia, qualitative changes in drug-binding sites, reductions in relative muscle mass, increases in the proportion of body fat, and decreases in total body water. The plasma level of free, active drug is often a direct function of the extent of drug binding to plasma proteins. There is a well-documented age-dependent decline (about 20%) in plasma albumin concentration in humans due to a reduced rate of hepatic albumin... 

Mintun, M., Raichle, M., Kilbourn, M., et al. A quantitative model for the in vivo assessment of drug binding sites with positron emission tomography. Ann. Neurol. 15, 217-227, 1984. 

Tantillo C, Ding J, Jacobo-Molina A, Nanni RG, Boyer PL, Hughes SH, et al. Locations of anti-AIDS drug binding sites and resistance mutations in the three-dimensional structure of HIV-1 reverse transcriptase implications for mechanisms of drug inhibition and resistance. J Mol Biol 1994 243 369-387. 

This pocket is inside the P barrel of VP1, directly underneath the canyon floor where ICAM-1 binds (Figure lc). The proximity of the hydrophobic drug-binding site to the receptor-binding site explains the effects these compounds have on viral attachment in specific HRV serotypes (see below). 

Table 1 Toxin and drug binding sites on a-subunits of voltage-gated sodium channels (Catterall, 1992).

L-type Ca2+ channels are the only VDCC which have three different drug binding sites, the... 

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