View source for 6xhe


==Structure of beta-prolinyl 5'-O-adenosine phosphoramidate==
<StructureSection load='6xhe' size='340' side='right'caption='[[6xhe]], [[Resolution|resolution]] 1.88&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XHE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XHE FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.88&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=V2J:5-O-[(S)-[(3S)-3-carboxypyrrolidin-1-yl](hydroxy)phosphoryl]adenosine'>V2J</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6xhe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xhe OCA], [https://pdbe.org/6xhe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xhe RCSB], [https://www.ebi.ac.uk/pdbsum/6xhe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xhe ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
Phosphoramidates composed of an amino acid and a nucleotide analogue are critical metabolites of prodrugs, such as remdesivir. Hydrolysis of the phosphoramidate liberates the nucleotide, which can then be phosphorylated to become the pharmacologically active triphosphate. Enzymatic hydrolysis has been demonstrated, but a spontaneous chemical process may also occur. We measured the rate of enzyme-free hydrolysis for 17 phosphoramidates of ribonucleotides with amino acids or related compounds at pH 7.5. Phosphoramidates of proline hydrolyzed fast, with a half-life time as short as 2.4 h for Pro-AMP in ethylimidazole-containing buffer at 37 degrees C; 45-fold faster than Ala-AMP and 120-fold faster than Phe-AMP. Crystal structures of Gly-AMP, Pro-AMP, betaPro-AMP and Phe-AMP bound to RNase A as crystallization chaperone showed how well the carboxylate is poised to attack the phosphoramidate, helping to explain this reactivity. Our results are significant for the design of new antiviral prodrugs.

The Enzyme-Free Release of Nucleotides from Phosphoramidates Depends Strongly on the Amino Acid.,Jovanovic D, Tremmel P, Pallan PS, Egli M, Richert C Angew Chem Int Ed Engl. 2020 Nov 2;59(45):20154-20160. doi:, 10.1002/anie.202008665. Epub 2020 Sep 15. PMID:32757352<ref>PMID:32757352</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6xhe" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Egli M]]
[[Category: Pallan PS]]