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Publication Abstract from PubMed

The crystal structures of protein-nucleic acid complexes are commonly determined using selenium-derivatized proteins via MAD or SAD phasing. Here, the first protein-nucleic acid complex structure determined using selenium-derivatized nucleic acids is reported. The RNase H-RNA/DNA complex is used as an example to demonstrate the proof of principle. The high-resolution crystal structure indicates that this selenium replacement results in a local subtle unwinding of the RNA/DNA substrate duplex, thereby shifting the RNA scissile phosphate closer to the transition state of the enzyme-catalyzed reaction. It was also observed that the scissile phosphate forms a hydrogen bond to the water nucleophile and helps to position the water molecule in the structure. Consistently, it was discovered that the substitution of a single O atom by a Se atom in a guide DNA sequence can largely accelerate RNase H catalysis. These structural and catalytic studies shed new light on the guide-dependent RNA cleavage.

Novel complex MAD phasing and RNase H structural insights using selenium oligonucleotides.,Abdur R, Gerlits OO, Gan J, Jiang J, Salon J, Kovalevsky AY, Chumanevich AA, Weber IT, Huang Z Acta Crystallogr D Biol Crystallogr. 2014 Feb;70(Pt 2):354-61. doi:, 10.1107/S1399004713027922. Epub 2014 Jan 29. PMID:24531469^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.