About: Complex between Human RNase HI and the phosphonate-DNA/RNA duplex: Molecular dynamics study

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rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
rdfs:seeAlso	http://dx.doi.org/10.1016/j.jmgm.2013.05.004
Description	Our 200 ns MD simulations show that even fully modified oligonucleotides bearing the 3'-O-P-CH2-O-5' (but not 3'-O-CH2-P-O-5') phosphonate linkages can be successfully attached to the surface of Human RNase H. It enables to explain that oligonucleotides consisting of the alternating 3'-O-P-CH2-O-5' phosphonate and phosphodiester linkages are capable to elicit the RNase H activity (while the 3'-O-CH2-P-O-5' phosphonates are completely inactive). Stability of the binuclear active site of Human RNase H was achieved using the one-atom model for Mg2+ in conjunction with a polarized phosphate group of the scissile bond, which is wedged between both magnesium ions. The reference MD simulation (lasting for 1000 ns), which was produced using a well-established seven-point (with dummy atoms) model for Mg2+ led to essentially the same results. The MD run (lasting for 500 ns) produced for the Therms thermophilus Argonaute enzyme shows the transferability of our approach for the stabilization of a binuclear active site. Glu512 was bound in the T. thermophilus Argonaute active site to the 2'-OH of the nucleotide adjacent to the scissile phosphate and one of the two active-site divalent metal ions in exactly the same way as Glu186 in Human RNase H. Glu512 thus completes the catalytic tetrad of Argonaute. Our 200 ns MD simulations show that even fully modified oligonucleotides bearing the 3'-O-P-CH2-O-5' (but not 3'-O-CH2-P-O-5') phosphonate linkages can be successfully attached to the surface of Human RNase H. It enables to explain that oligonucleotides consisting of the alternating 3'-O-P-CH2-O-5' phosphonate and phosphodiester linkages are capable to elicit the RNase H activity (while the 3'-O-CH2-P-O-5' phosphonates are completely inactive). Stability of the binuclear active site of Human RNase H was achieved using the one-atom model for Mg2+ in conjunction with a polarized phosphate group of the scissile bond, which is wedged between both magnesium ions. The reference MD simulation (lasting for 1000 ns), which was produced using a well-established seven-point (with dummy atoms) model for Mg2+ led to essentially the same results. The MD run (lasting for 500 ns) produced for the Therms thermophilus Argonaute enzyme shows the transferability of our approach for the stabilization of a binuclear active site. Glu512 was bound in the T. thermophilus Argonaute active site to the 2'-OH of the nucleotide adjacent to the scissile phosphate and one of the two active-site divalent metal ions in exactly the same way as Glu186 in Human RNase H. Glu512 thus completes the catalytic tetrad of Argonaute. (en)
Title	Complex between Human RNase HI and the phosphonate-DNA/RNA duplex: Molecular dynamics study Complex between Human RNase HI and the phosphonate-DNA/RNA duplex: Molecular dynamics study (en)
skos:prefLabel	Complex between Human RNase HI and the phosphonate-DNA/RNA duplex: Molecular dynamics study Complex between Human RNase HI and the phosphonate-DNA/RNA duplex: Molecular dynamics study (en)
skos:notation	RIV/00216208:11320/13:10190058!RIV14-GA0-11320___
http://linked.open...avai/riv/aktivita	I P
http://linked.open...avai/riv/aktivity	I, P(GA202/09/0193)
http://linked.open...iv/cisloPeriodika	červenec
http://linked.open...vai/riv/dodaniDat	2014
http://linked.open...aciTvurceVysledku	Barvík, Ivan Maláč, Kamil
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Univerzita Karlova v Praze / Matematicko-fyzikální fakulta
http://linked.open...dnocenehoVysledku	66442
http://linked.open...ai/riv/idVysledku	RIV/00216208:11320/13:10190058
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	ACEMD; Molecular dynamics; Phosphonate; RNAi; Argonaute; Antisense oligonucleotides; RNase H (en)
http://linked.open.../riv/klicoveSlovo	ACEMD Antisense oligonucleotides Phosphonate RNase H Molecular dynamics RNAi Argonaute
http://linked.open...odStatuVydavatele	US - Spojené státy americké
http://linked.open...ontrolniKodProRIV	[ABE20BF50D41]
http://linked.open...i/riv/nazevZdroje	Journal of Molecular Graphics and Modelling
http://linked.open...in/vavai/riv/obor	BO
http://linked.open...ichTvurcuVysledku	2 (xsd:int)
http://linked.open...cetTvurcuVysledku	2 (xsd:int)
http://linked.open...vavai/riv/projekt	Formation and dynamics of nucleic acid motifs involved in regulation of gene expression
http://linked.open...UplatneniVysledku	2013
http://linked.open...v/svazekPeriodika	44
http://linked.open...iv/tvurceVysledku	Barvík, Ivan Maláč, Kamil
http://linked.open...ain/vavai/riv/wos	000324965300009
issn	1093-3263
number of pages	10 (xsd:int)
http://bibframe.org/vocab/doi	10.1016/j.jmgm.2013.05.004
http://localhost/t...ganizacniJednotka	11320

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