8ub0 | pdb_00008ub0
Structure of Histidine-5'-O-adenosine phosphoramidate/RNase A
Structural highlights
FunctionRNAS1_BOVIN Endonuclease that catalyzes the cleavage of RNA on the 3' side of pyrimidine nucleotides. Acts on single stranded and double stranded RNA.[1] Publication Abstract from PubMedNucleoside monophosphates (NMPs) are the subunits of RNA. They are incorporated into growing complementary strands when sequences are copied in enzyme-free reactions using organic leaving groups at the phosphates. Amino acids are rarely considered as leaving groups, but proline can act as a leaving group when N-linked to NMPs, so that prolinyl NMPs hydrolyze in aqueous buffer at 37 degrees C, with half-life times as short as 2.4 h, and they act as monomers in enzyme-free primer extension. Still, their level of reactivity is insufficient for practical purposes, requiring months for some extensions. Herein we report the synthesis of eight substituted prolinyl AMPs together with seven related compounds and the results of a study of their reactivity. A delta-carboxy prolinyl NMP was found to be converted with a half-life time of just 11 min in magnesium-free buffer, and a delta-isopropyl prolinyl NMP was shown to react sevenfold faster than its prolinyl counterpart in enzyme-free genetic copying of RNA. Our results indicate that both anchimeric and steric effects can be employed to increase the reactivity of aminoacidyl nucleotides, i.e. compounds that combine two fundamental classes of biomolecules in one functional entity. Prolinyl Phosphoramidates of Nucleotides with Increased Reactivity.,Humboldt A, Rami F, Topp FM, Arnold D, Gohringer D, Pallan PS, Egli M, Richert C Angew Chem Int Ed Engl. 2024 Apr 8;63(15):e202319958. doi: , 10.1002/anie.202319958. Epub 2024 Feb 20. PMID:38300702[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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