8UAX
Structure of Alanyl-5'-O-adenosine phosphoramidate/RNase A
Summary for 8UAX
| Entry DOI | 10.2210/pdb8uax/pdb |
| Descriptor | Ribonuclease pancreatic, DI(HYDROXYETHYL)ETHER, (2S)-2-{[(R)-{[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl]amino}propanoic acid (non-preferred name), ... (4 entities in total) |
| Functional Keywords | rnase-a, nucleotide prodrug, amino acidyl phosphoramidate, alanyl-5'-amp, phosphoramidate hydrolysis, hydrolase, protide |
| Biological source | Bos taurus (cattle) |
| Total number of polymer chains | 2 |
| Total formula weight | 28153.31 |
| Authors | |
| Primary citation | Humboldt, A.,Rami, F.,Topp, F.M.,Arnold, D.,Gohringer, D.,Pallan, P.S.,Egli, M.,Richert, C. Prolinyl Phosphoramidates of Nucleotides with Increased Reactivity. Angew.Chem.Int.Ed.Engl., 63:e202319958-e202319958, 2024 Cited by PubMed Abstract: Nucleoside 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 °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 δ-carboxy prolinyl NMP was found to be converted with a half-life time of just 11 min in magnesium-free buffer, and a δ-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. PubMed: 38300702DOI: 10.1002/anie.202319958 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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