Structure, of P-glycoprotein

Lee, J.Y., Urbatsch, I.L., Senior, A.E. and Wilkens, S. (2002) Projection structure of P-glycoprotein by electron microscopy. Evidence for a closed conformation of the nucleotide binding domains. Journal of Biological Chemistry, 277, 40125-40131. 

Rosenberg, M.F., Callaghan, R., Modok, S., Higgins, C.F. and Ford, R.C. (2005) Three-dimensional structure of P-glycoprotein. Journal of Biological Chemistry, 280, 2857-2862. 

The structure of P-glycoprotein has not been determined. However, X-ray crystallographic structures have been determined for bacterial members of the ABC transporter family the MsbA lipid A "flippases" from E. coli (72) and Vibrio cholera (73) and the cobal-amin uptake transporter BtuCD protein of E. coli (74). These structures are consistent with the overall picture of P-glycoprotein function described here. 

Aller, S.G., Yu, J., Ward, A., Weng, Y, Chittaboina, S., Zhuo, R., Harrell, P.M., Trinh, YT, Zhang, Q., Urbatsch, I.L., and Chang, G. (2009) Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science, 323, 1718-1722. 

Ekins S, Kim RB, Leake BE, Dantzig AH, Schuetz E, Lan LB, et al. Application of three dimensional quantitative structure-activity relationships of P-glycoprotein inhibitors and substrates. Mol Pharmacol 2002 61 974-981. 

Yates CR, Chang C, Kearbey JD, Yasuda K, Schuetz EG, Miller DD, et al. Structural determinants of P-glycoprotein-mediated transport of glucocorticoids. Pharm Res 2003 20 1794-803. 

Three-dimensional quantitative structure-activity relationships of inhibitors of P-glycoprotein, Molec. Pharmacol. 2002, 61, 964-973. 

Seelig, A., Landwojtowicz, E., Structure-activity relationship of P-glycoprotein substrates and modifiers, Eur. J. Pharm. Sci. 2000, 12, 31—40. 

Skovsgaard, T., Stein, W. D., Structure—activity relationships of P-glycoprotein interacting drugs kinetic characterization of their effects on ATPase activity, Biochim. Biophys. Acta... 

Stouch, T. R., Gudmundsson, O., Progress in understanding the structure-activity relationships of P-glycoprotein, Adv. Drug Deliv. Rev. 2002, 54, 315-328. 

Detailed structure-activity relationships of P-glycoprotein are not yet available. Some understanding is provided by Seelig [12] who has compared structural features in P-glycoprotein substrates. This analysis has indicated that recognition elements are present in structures and are formed by two (type I) or three electron donor groups (type II) with a fixed spatial separation. The type I element consists of two electron donor groups separated by 2.5 A, whilst the type II elements has a spatial... 

Wang, R.B., Kuo, C.L, Lien, L.L, and Lien, E.J. (2003) Structure activity relationship analysis of P-glycoprotein substrates and inhibitafsClin. Pharm. Ther., 28 203-228. 

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