SRIPATHI, Kamali N., Pavel BANÁŠ, Kamila RÉBLOVÁ, Jiří ŠPONER, Michal OTYEPKA a Nils G. WALTER. Wobble pairs of the HDV ribozyme play specific roles in stabilization of active site dynamics. Physical Chemistry Chemical Physics. CAMBRIDGE: ROYAL SOC CHEMISTRY, 2015, roč. 17, č. 8, s. 5887-5900. ISSN 1463-9076. doi:10.1039/c4cp05083e.
Další formáty:   BibTeX LaTeX RIS
Základní údaje
Originální název Wobble pairs of the HDV ribozyme play specific roles in stabilization of active site dynamics
Autoři SRIPATHI, Kamali N. (840 Spojené státy), Pavel BANÁŠ (203 Česká republika), Kamila RÉBLOVÁ (203 Česká republika, domácí), Jiří ŠPONER (203 Česká republika, garant, domácí), Michal OTYEPKA (203 Česká republika) a Nils G. WALTER (840 Spojené státy).
Vydání Physical Chemistry Chemical Physics, CAMBRIDGE, ROYAL SOC CHEMISTRY, 2015, 1463-9076.
Další údaje
Originální jazyk angličtina
Typ výsledku Článek v odborném periodiku
Obor 10403 Physical chemistry
Stát vydavatele Velká Británie
Utajení není předmětem státního či obchodního tajemství
WWW URL
Impakt faktor Impact factor: 4.449
Kód RIV RIV/00216224:14740/15:00082900
Organizační jednotka Středoevropský technologický institut
Doi http://dx.doi.org/10.1039/c4cp05083e
UT WoS 000349697200043
Klíčová slova anglicky HEPATITIS-DELTA-VIRUS; SELF-CLEAVING RIBOZYMES; ACID-BASE CATALYSIS; MOLECULAR-DYNAMICS; CONFORMATIONAL SWITCH; CLEAVAGE ACTIVITY; METAL-ION; MECHANISTIC CHARACTERIZATION; CRYSTAL-STRUCTURE; GENOMIC RIBOZYME
Štítky podil, rivok
Příznaky Mezinárodní význam, Recenzováno
Změnil Změnila: Mgr. Eva Špillingová, učo 110713. Změněno: 29. 3. 2016 15:22.
Anotace
The hepatitis delta virus (HDV) is the only known human pathogen whose genome contains a catalytic RNA motif (ribozyme). The overall architecture of the HDV ribozyme is that of a double-nested pseudoknot, with two GU pairs flanking the active site. Although extensive studies have shown that mutation of either wobble results in decreased catalytic activity, little work has focused on linking these mutations to specific structural effects on catalytic fitness. Here we use molecular dynamics simulations based on an activated structure to probe the active site dynamics as a result of wobble pair mutations. In both wild-type and mutant ribozymes, the in-line fitness of the active site (as a measure of catalytic proficiency) strongly depends on the presence of a C75(N3H3+)N1(O5') hydrogen bond, which positions C75 as the general acid for the reaction. Our mutational analyses show that each GU wobble supports catalytically fit conformations in distinct ways; the reverse G25U20 wobble promotes high in-line fitness, high occupancy of the C75(N3H3+)G1(O5') general-acid hydrogen bond and stabilization of the G1U37 wobble, while the G1U37 wobble acts more locally by stabilizing high in-line fitness and the C75(N3H3+)G1(O5') hydrogen bond. We also find that stable type I A-minor and P1.1 hydrogen bonding above and below the active site, respectively, prevent local structural disorder from spreading and disrupting global conformation. Taken together, our results define specific, often redundant architectural roles for several structural motifs of the HDV ribozyme active site, expanding the known roles of these motifs within all HDV-like ribozymes and other structured RNAs.
Návaznosti
ED1.1.00/02.0068, projekt VaVNázev: CEITEC - central european institute of technology
VytisknoutZobrazeno: 16. 8. 2022 07:09