Rotamases

Peptidyl-prolyl cis-trans isomerase A (Rotamase) P05092 3X 2X... 

While indirect selections work quite well for antibodies they have been less successful in the case of catalytic nucleic acids. There are only three examples which prove that it is possible in principle to obtain a ribo- or deoxyribozyme by selecting an aptamer that binds to a TSA A rotamase ribozyme [7], a ribozyme capable of catalyzing the metallation of a porphyrin derivative [92], and one catalytic DNA of the same function [93]. Another study reported the selection of a population of RNA-aptamers which bind to a TSA for a Diels-Alder reaction but the subsequent screen for catalytic activity was negative for all individual RNAs tested [94]. The attempt to isolate a transesterase ribozyme using the indirect approach also failed [95]. 

Stefan Fischer, Curvilinear reaction-coordinates of conformal change in macromolecules application to rotamase catalysis , Ph. D. Thesis, Harvard University, (1992). 

It was a surprise to discover that all of the cyclo-philins and FK506-binding proteins are peptidyl prolyl cis—traits isomerases or rotamases. They all catalyze the following simple and reversible reaction of a prolyl peptide linkage ... 

Rocky Mountain spotted fever 7 Rods (visual receptor cells) 390 Root hairs, dimensions of 30 Roseoflavin 788, 789s Rossmann fold. See Nucleotide-binding domain Rotamases 488 Rotary diffusion constant 463 Rotation of molecules 462,463 Rotational barrier 44 Rotifers 24, 25... 

In 1991 the focus of immunosuppression caused by FK506 or CsA shifted away from their immediate immunophilin targets and associated rotamase activities and toward a common target that was identified downstream of the initial immunosuppressant-immunophilin interaction. In a seminal report, Schreiber and colleagues showed that either immobi-... 

Irreversible Inhibition of Enzymes 488 Box9-F Immunophilins as Rotamases... 

Fischer, S., Michnick, S. and Karplus, M. (1993) A Mechanism for Rotamase Catalysis by the FK506 Binding Protein (FKBP), Biochemistry 32, 13830-13837. 

Orozco, M.,Tirado-Rives, J., and Jorgensen, W.L. (1993) Mechanism for the rotamase activity of FK506 binding protein from molecular dynamics simulations. Biochemistry 32, 12864-12874. 

Figure 1.23 SMase inhibitors (42) and FKBP 12 rotamase inhibitors (43). Numbers within the parentheses are IC50 values.

Rosen, M. K Standaert, R. F Galat, A., Nakatsuka, M Schreiber, S. L. (1990). Inhibition of FKBP rotamase activity by immunosuppressant FK506 twisted amide surrogate. Science, 248, 863-866. 

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