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1 rientation of the three helical stems in the hammerhead.
2 mation observed in crystal structures of the hammerhead.
3 ations corresponding to > 8-9 Mn2+ bound per hammerhead.
4 multimers of satRPV RNA cleave via a double hammerhead.
5 lts in an increased number of bound Mn2+ per hammerhead.
6 that may facilitate formation of the double hammerhead.
7 en cleavage and ligation for the Schistosoma hammerhead.
8 e cleavage properties of chemically modified hammerheads.
9 Chimeras of the well-characterized minimal hammerhead 16 and nine extended hammerheads derived from
10 SV (+) hammerhead and the well-characterized hammerhead 16 were used to measure the cleavage rate con
12 is fully stabilized at >2.5 mM MgCl(2) while hammerhead activity continues to increase with an increa
13 affinities determined by EPR indicates that hammerhead activity in 0.1 M NaCl is only observed after
14 oincides with Co(NH(3))(6)(3+) inhibition of hammerhead activity in 500 microM Mn(2+), reducing the a
19 o different chimeras combining the sTRSV (+) hammerhead and the well-characterized hammerhead 16 were
20 e chimeras were all more active than minimal hammerheads and exhibited a very broad range of catalyti
24 RNAiFold to design a functional cis-cleaving hammerhead as a modular unit of a synthetic larger RNA.
26 of cleavage and the fraction of full-length hammerhead at equilibrium and thereby deduce the element
27 he coupling between slow modes involving the hammerhead backbone with fast modes in the cleavage site
29 croM Mn(2+), reducing the activity of the WT hammerhead by approximately 15-fold with an inhibition c
30 t that residues involved in the chemistry of hammerhead catalysis are likely located in that region c
31 kinetic analysis to test the hypothesis that hammerhead catalysis occurs by a general acid-base mecha
35 rent from, similar experiments examining the hammerhead cleavage properties of the R(P)-phosphoromono
36 ogsteen face of G12, the general base in the hammerhead cleavage reaction, thereby potentially dissip
38 ate of dissociation of P1, the 5' product of hammerhead cleavage, is 100-300-fold slower in full-leng
39 hat the O2-carbonyl of the U4 residue of the hammerhead complex is critical for transition state stab
44 cross-linking analysis of native and minimal hammerheads containing photoreactive nucleobases 6-thiog
45 method, we show that tertiary folding of the hammerhead core occurs with a highly unfavorable enthalp
46 t a model for the ion-induced folding of the hammerhead core that is similar to those advanced for th
47 athway is that it initiates from the minimal hammerhead crystal structure and describes the reaction
48 op I-loop II interaction, an extended format hammerhead derived from sTRSV studied here shows at leas
49 ized minimal hammerhead 16 and nine extended hammerheads derived from natural viroids and satellite R
50 that combines the scoring function from the Hammerhead docking system with a search engine that reli
53 results support a model in which the native hammerhead folds to an active structure similar to that
56 se results have general implications, as the hammerhead, hairpin, and twister ribozymes have guanines
58 anisms of four small self-cleaving RNAs: the hammerhead, hairpin, hepatitis delta virus, and in vitro
61 explored via the assembly of several altered hammerhead (HH) ribozymes and a singly modified HH subst
64 7 is buried within the catalytic core of the hammerhead in the X-ray structure, we propose that the e
67 ather, the cross-link constrains the cleaved hammerhead into a structure that more closely resembles
68 cleophilic attack is taken into account, the hammerhead is remarkably effective at cleaving the dithi
69 d conformation of the catalytic core of this hammerhead, leading to a ribozyme that is readily cleave
70 s are consistent with the currently accepted hammerhead-like mechanism of cleavage, they do not add d
72 or experiments directed at understanding the hammerhead mechanism and the role of the loop I-loop II
73 requirement, the Mn2+-binding properties of hammerhead model ribozymes have been investigated under
78 rast to the previously identified continuous hammerheads, occur as two fragments separated by hundred
80 een base-pairing interaction, in full-length hammerheads possessing this interaction, is sufficient f
81 etter ligase than it is a nuclease while the hammerhead reaction favors cleavage over ligation of bou
82 dditional differences in the behavior of the hammerhead relative to that of protein enzymes and large
83 previously determined that, in solution, the hammerhead ribozyme (a self-cleaving RNA) has a high-aff
84 eloped a recombinant adenovirus expressing a hammerhead ribozyme (AdRZ) targeted against the porcine
85 fects at the C3, G8, and G5 positions of the hammerhead ribozyme (HHR) are reported, based on a serie
86 ) and divalent (Mg(2+)) metal ion binding in hammerhead ribozyme (HHR) has been explored with molecul
87 ional RNAs in these microbiomes, we used the hammerhead ribozyme (HHR) motif to search for sequences
89 ractions with the cleavage site of a minimal hammerhead ribozyme (mHHRz) were probed using (31)P NMR-
90 ent VPAC1- or VPAC2-selective antagonists, a hammerhead ribozyme (Rz) strategy capable of in vivo app
92 te that, over this NaCl concentration range, hammerhead ribozyme activity is influenced by population
94 ate-limiting step in the synthesis of GSH, a hammerhead ribozyme against gamma-GCS mRNA to downregula
96 -dependent cleavage between G8 and A9 in the hammerhead ribozyme and have discovered that U4 cleavage
97 tical assays to detect chemically stabilized hammerhead ribozyme and putative ribozyme metabolites fr
100 that are proposed to bind metal ions in the hammerhead ribozyme are the A9/G10.1 site, located at th
101 ructure of the enzyme-product complex of the hammerhead ribozyme by using a reinforced crystal lattic
102 therefore conclude that such a mechanism of hammerhead ribozyme catalysis is untenable, at least in
109 ich the stable ground state structure of the hammerhead ribozyme complexed with the substrate is a pa
110 exogenous c-fms-transfected microglia with a hammerhead ribozyme compromised their neuroprotective pr
112 c transfer RNA from budding yeast and of the hammerhead ribozyme demonstrate the applicability of the
113 The recent X-ray crystal structure of a hammerhead ribozyme derived from Schistosoma mansoni con
114 ave obtained a 1.55-A crystal structure of a hammerhead ribozyme derived from Schistosoma mansoni und
115 ith green fluorescent protein reporter and a hammerhead ribozyme directed against caspase-3 mRNA.
118 tions or changes are required in the minimal hammerhead ribozyme enzyme strand sequence (providing th
119 al binding site is uniquely populated in the hammerhead ribozyme even in a background of high ionic s
125 metal (Mg(2+)) ion-dependent folding of the hammerhead ribozyme from Schistosoma mansoni was monitor
130 l change equivalent to that observed for the hammerhead ribozyme having an unmodified attacking nucle
131 for the highest affinity Mn(2+) site in the hammerhead ribozyme in 1 M NaCl, tentatively attributed
132 Cleavage of the corresponding unmodified hammerhead ribozyme in the crystal under otherwise ident
133 gen receptor with an antibody and an AR mRNA hammerhead ribozyme in the following cell lines: LNCaP (
141 est whether the Y-shaped conformation of the hammerhead ribozyme is maintained throughout the catalyt
144 Based on this result, we developed a double hammerhead ribozyme long-term expression system to silen
147 gest that Mg2+ is profoundly involved in the hammerhead ribozyme mechanism both at structural and cat
149 at, under near-physiological conditions, the hammerhead ribozyme motif is the most common (and thus t
151 rus genomic RNA (PKB134) and the alternative hammerhead ribozyme pseudoknot (PKB173), both of which a
156 ining step under standard conditions for the hammerhead ribozyme self-cleavage reaction, and that an
157 own of SPF45 in parental A2780 cells using a hammerhead ribozyme sensitized A2780 cells to etoposide
159 slope of 0.7, as has been observed for other hammerhead ribozyme sequences in solution, indicating th
160 ErbB-4 receptors in breast cancer, we used a hammerhead ribozyme strategy to achieve down-regulation
161 fragment pair can assemble to form an active hammerhead ribozyme structure between the translation te
162 ation of a hypothesized catalytically active hammerhead ribozyme structure in which a single divalent
164 unlike in solution where this and most other hammerhead ribozyme substrates are cleaved only to about
166 ructure of a full-length Schistosoma mansoni hammerhead ribozyme that permits us to explain the struc
167 observed 7.8 A conformational change in the hammerhead ribozyme that positions the substrate for in-
168 fficking of HIV-1 RNAs into the nucleolus, a hammerhead ribozyme that specifically cleaves HIV-1 RNA
170 porcine PCNA gene and constructed a chimeric hammerhead ribozyme to a segment of the gene with human
171 ous Bcl-2, an adenoviral vector expressing a hammerhead ribozyme to Bcl-2 (Ad-Rbz-Bcl-2) mRNA was emp
172 e elements of the isoleucine aptamer and the hammerhead ribozyme to estimate the probability that a s
173 tate of RNA and by employing a self-cleaving hammerhead ribozyme to investigate the degradative conse
175 d those 5'-end extra nucleotides utilizing a hammerhead ribozyme to produce transcripts with accurate
176 wth and differentiation of APL cells using a hammerhead ribozyme to target PML/RAR alpha mRNA in the
177 teen base-pairing interaction in the minimal hammerhead ribozyme transforms an RNA sequence possessin
179 es in internal structure and dynamics of the hammerhead ribozyme upon metal ion induced folding, chan
180 catalytic conformational intermediate of the hammerhead ribozyme using a phosphodiester tether formed
181 using an anti-erb B-4 blocking antibody or a hammerhead ribozyme vector targeted to erb B-4 mRNA, imp
182 t a cross-link between stems I and II of the hammerhead ribozyme was confirmed and further explored.
183 f mutant RET could prevent transformation, a hammerhead ribozyme was designed to cleave RET mRNA cont
186 pport the catalytic site of a minimal type I hammerhead ribozyme were replaced with oligo-U loops, se
188 unction, transcripts were used to assemble a hammerhead ribozyme with all permutations of natural and
189 ermodynamic dissection of the folding of the hammerhead ribozyme, a three-way RNA helical junction, b
190 revious observations in X-ray studies of the hammerhead ribozyme, and emphasizes the necessity for dy
191 structure of a small self-cleaving RNA, the hammerhead ribozyme, both prevents and enhances RNA auto
192 igation is less for the hairpin than for the hammerhead ribozyme, consistent with the notion that a m
193 e synthesize a significant part of an active hammerhead ribozyme, forging a link between nonenzymatic
196 d the results are compared with those of the hammerhead ribozyme, which has similar size and secondar
197 GFP-like Spinach aptamer and a highly active hammerhead ribozyme, which is appended to the RNA of int
198 nsequence of the very early evolution of the hammerhead ribozyme, with all extant examples being desc
200 ave used photocrosslinking as a tool to trap hammerhead ribozyme-substrate complexes in various stage
223 Other approaches have included the use of hammerhead ribozymes against the MDR-1 gene and MDR-1-ta
228 In addition, they demonstrate the utility of hammerhead ribozymes as a simple, effective and easily a
230 e catalytic activity of these Se-derivatized hammerhead ribozymes by cleaving the RNA substrate, and
233 4M act as functional switches in a family of hammerhead ribozymes deactivated by stem or loop replace
236 We have solved two crystal structures of hammerhead ribozymes having 2'-OCH(3) or 2'-F substituti
238 ations of the native and mutated full length hammerhead ribozymes in the reactant state and in an act
242 o modulate apoB gene expression, we designed hammerhead ribozymes targeted at AUA(6665) and GUA(6679)
243 ell lines were made that expressed antisense-hammerhead ribozymes targeted specifically against TIF1b
245 (HCV) infection, we designed and synthesized hammerhead ribozymes targeting 15 conserved sites in the
246 ysis, we have created a series of allosteric hammerhead ribozymes that are activated by theophylline.
247 s used to isolate five classes of allosteric hammerhead ribozymes that are triggered by binding to ce
254 n RNA switch, (ii) self-functional elements (hammerhead ribozymes), and (iii) cis-acting elements tha
255 Using RNAiFold, we design ten cis-cleaving hammerhead ribozymes, all of which are shown to be funct
258 e-responsive, in vivo functional, allosteric hammerhead ribozymes, this work describes a general appr
259 tter understand the observed distribution of hammerhead ribozymes, we used in vitro selection to sear
260 rom the primary transcript by two cis-acting hammerhead ribozymes, yielding the required engineered e
268 pears to mimic interactions in the wild-type hammerhead RNA that enable switching between nuclease an
269 at is instead typical of full-length natural hammerhead RNAs that have additional extensive tertiary
271 age, resulting in liberation of the internal hammerhead Rz, which we targeted to a single-stranded re
272 d by using random-sequence bridges to join a hammerhead self-cleaving ribozyme to an aptamer from a n
273 erved in all naturally occurring full-length hammerhead sequences have evolved to prevent deleterious
278 any of the disagreements between the minimal hammerhead structure and the biochemical data on the cle
280 MgCl(2) concentration, it is clear that the hammerhead structure in the transition state must differ
281 ies, our thermodynamic data suggest that the hammerhead structure is stabilized in vitro predominantl
286 Analysis of kinetics on this small set of hammerheads suggests that cleavage rate of computational
287 avage, is 100-300-fold slower in full-length hammerheads than in hammerheads that either lack or have
288 ld slower in full-length hammerheads than in hammerheads that either lack or have disrupting mutation
290 atalytic diversity is observed among minimal hammerheads that lack the tertiary interactions, a possi
292 oach and stack upon G8 and G12 of the native hammerhead, two conserved nucleobases that show similar
295 , these results support a model in which the hammerhead undergoes a transient conformational change i
297 full-length satRPV RNA and two copies of the hammerhead, wild-type RNA cleaves much more efficiently
299 n the rate of ligation compared to a minimal hammerhead without the loop-loop tertiary interaction, y
300 ysts that include the hepatitis delta virus, hammerhead, X motif and Tetrahymena group I ribozymes, a
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