Cryptic binding site

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]. 

Eg5 (Motor Protein and Mitotic Kinesin) -Accessible Active Site, More Amenable Cryptic Binding Site... 

Tsurupa, G., and Medved, L. (2001). Fibrinogen alpha C domains contain cryptic plasminogen and tPA binding sites. Ann. NY Acad. Sci. 936, 328-330. 

Grimsley, J.K., Calamini, B., Wild, J.R., Mesecar, A.D. (2005). Structural and mutational studies of organophosphorus hydrolase reveal a cryptic and functional allosteric-binding site. Arch. Biochem. Biophys. 442 169-79. 

Palmer, C.N., M.H. Hsu, A.S. Muerhoff, K.J. Griffin and E.F. Johnson. Interaction of the peroxisome proliferator-activated receptor alpha with the retinoid X receptor alpha unmasks a cryptic peroxisome proliferator response element that overlaps an ARP-1 binding site in the CYP4A6 promoter. J. Biol. Chem. 269 18083-18089, 1994. 

McLean LR, Zhang Y, Li H et al (2010) Fragment screening of inhibitors for MIF tautomer-ase reveals a cryptic surface binding site. Bioorg Med Chem Lett 20 1821-1824... 

Ponniah S, Endres RO, Hasty DL et al. (1991) Fragmentation of Escherichia coli type 1 fimbriae exposes cryptic D-mannose-binding sites. J Bacteriol 173 4195—4202... 

Sung, U., O Rear, J.J. and Yurchenco, P.D. (1993) Cell and heparin-binding sites in the distal long arm of laminin identification of active and cryptic sites with recombinant and hybrid glycoprotein. J. Cell Biol. 123 1255-1268. 

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