Ribozymes hairpin ribozyme

The ribozymes were widely modified and can be further subdivided according to their structural features in group I ribozymes, hammerhaed ribozymes, hairpin ribozymes, ribonucelase P (RNase P), and hepatitis delta virus ribozymes. 

To date, RNA calculations have been performed on a variety of systems of different topologies including helical duplexes, hairpin loops, and single strands from tRNA, rRNA, and ribozymes. In a simulation of an RNA tetraloop of the GRNA type, which is very common and known to be remarkably stable, it was found that without imposing any external infonnation the simulation found the right confonnation even when it started from the wrong one [72]. Studies have used Ewald summation methods to handle the... 

Yamada O, Yu M, Yee JK, Kraus G, Looney D, Wong-Staal F (1994) Intracellular immunization of human T cells with a hairpin ribozyme against human immunodeficiency virus type 1, Gene Ther 1 38 5... 

Case Study Chemical Steps of Catalysis in Hairpin Ribozyme... 

In contrast, the hairpin ribozyme (HPR) [107, 108], which catalyzes the reversible, site-specific phosphodiester bond cleavage of an RNA substrate, is unique in that the chemical steps of the reaction do not require involvement of a divalent metal ion [107-111]. This lack of an explicit metal ion requirement [112] makes the hairpin ribozyme an ideal target for theoretical studies aimed to characterize the contribution of generalized solvation provided by the solvated ribozyme on catalysis. 

Scheme 14-1. General in-line monoanionic mechanism of phosphodiester cleavage transesterification catalyzed by hairpin ribozyme the first proton transfer (PT1), the nucleophilic attack (Nu), and the exocyclic cleavage (Cl) steps are shown, and the Oip and O2p pathways are indicated by blue and red colored hydrogens, respectively. For the uncatalyzed model reaction in solution, the Ojp and O2p pathways are energetically equivalent...

Figure 14-6. Two-dimensional free energy surfaces for in-line monoanionic mechanisms for the (A) un-catalytic model reaction in solution, and the catalytic (B) O p and (C) O2p pathways in the hairpin ribozyme. fi is defined as Rp-o5, R02,-P> and 2 is R02,-H2, rOnb-H2, for fl < 0.0 A and r05,-H2, rOnb-H2, f°r 1 > 0.0 A, where Opjg is for the G p proton transfer in (B), and for the O2p proton transfer in (A) and (C), respectively. The units for free energies and distances are kcal/mol and A, respectively...

CA DFT correction on the TSp u is based on the error of AMl/d-PhoT model at the TSpti+Nu> 1 n which the nucleophilic attack (TS ra) is concerted with the proton transfer (TS/>/ ] ) in the gas phase. dUncatalyzed model reaction in solution. eCatalyzed reaction in the hairpin ribozyme. 

Experimental values for the hairpin ribozyme are taken from references [113—115]. 

Figure 14-7. Snapshots of the active site structures near the transition state of (top) the nucleophilic attack and (bottom) the exocyclic cleavage for the in-line monoanionic O2p mechanism of cleavage transesterification in the hairpin ribozyme. The yellow and red colored cartoon is for the substrate and ribozyme strands, respectively, and water molecules interacting with non-bridging oxygens and O5/ are shown...

Lilley DM (2008) Ribozymes and RNA Catalysis, chap. The Hairpin and Varkud Satellite Ribozymes, 66-91, RSC Biomolecular Series, RSC Publishing, Cambridge. 

However, there are a number of other miscellaneous biological roles played by this complex. The [Co(NH3)6]3+ ion has been shown to inhibit the hammerhead ribozyme by displacing a Mn2+ ion from the active site.576 However, [Co(NH3)6]3+ does not inhibit ribonuclease H (RNase),577 topoisomerase I,578 or hairpin ribozyme,579 which require activation by Mg2+ ions. The conclusions from these studies were that an outer sphere complex formation between the enzyme and Mgaq2+ is occuring rather than specific coordination of the divalent ion to the protein. These results are in contrast to DNase I inhibition by the same hexaammine complex. Inhibition of glucose-induced insulin secretion from pancreatic cells by [Co(NH3)6]3+ has been found.580 Intracellular injection of [Co(NH3)6]3+ into a neurone has been found to cause characteristic changes to the structure of its mitochondria, and this offers a simple technique to label neuronal profiles for examination of their ultrastructures.581... 

Another naturally occurring ribozyme which catalyzes phosphodiester transfer reactions is the hairpin ribozyme. The hairpin ribozyme has been the subject of a number of excellent review articles [24,25]. Several independent studies performed recently have indicated that the hairpin ribozyme has an interesting feature which distinguishes it from the aforementioned ribozymes mechanistically While the HHR, the group I intron, the HDV ribozyme and many other ribozymes that we are going to meet in this review are metalloenzymes and require divalent metal ions in their active sites for functional group activation, divalent metals ions only play a passive role (they are mainly required for cor-... 

Burke JM, Butcher SE, SargueU B (1996). Structural analysis and modifications of the hairpin ribozyme, p 129-144. In Eckstein F, Lilley DMJ (ed) Catalytic RNA, vol. 10. Springer, Berlin Heidelberg New York... 

Fig. 1A-F The two-dimensional structures of various ribozymes. The ribozyme or intron portion is printed in black. The substrate or exon portion is printed in gray. Arrows indicate sites of cleavage by ribozymes A (left) the two-dimensional structure of a hammerhead ribozyme and its substrate. Outlined letters are conserved bases that are involved in catalysis right) The y-shaped structure of the hammerhead ribozyme-sub-strate complex B-F the two-dimensional structures of a hairpin ribozyme, the genomic HDV ribozyme, a group I ribozyme from Tetrahymena, a group II ribozyme from S. cer-evisiae (aiy5), and the ribozyme of RNase P from E. coli...

Fig. 10A pL (L=H or D) profiles of hairpin ribozyme of the native sequence of and 2,6-diaminopurine at position 8 [119]. The native sequence in H2O and in D2O are represented hy filled diamonds and filled squares, respectively. 2,6-diaminopurine at position 8 in H2O and in D2O are represented by open circles and open triangles, respectively. B Proposed catalytic mechanism. RNA cleavage catalyzed by the keto-enol tautomeriza-tion of Gg is achieved by a abstraction of a proton from the N1 to the 5 -0 leaving group [119]... 

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