View source for 9qtc


==HINT1 complexed with GS-441524==
<StructureSection load='9qtc' size='340' side='right'caption='[[9qtc]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9qtc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9QTC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9QTC 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]] 1.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=U08:(2~{R},3~{R},4~{S},5~{R})-2-(4-azanylpyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-(hydroxymethyl)-3,4-bis(oxidanyl)oxolane-2-carbonitrile'>U08</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=9qtc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9qtc OCA], [https://pdbe.org/9qtc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9qtc RCSB], [https://www.ebi.ac.uk/pdbsum/9qtc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9qtc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HINT1_HUMAN HINT1_HUMAN] Hydrolyzes adenosine 5'-monophosphoramidate substrates such as AMP-morpholidate, AMP-N-alanine methyl ester, AMP-alpha-acetyl lysine methyl ester and AMP-NH2 (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Remdesivir is an antiviral ProTide-type nucleotide analog, which is activated into its 5'-triphosphate form by several cellular enzymes. The human histidine triad nucleotide-binding protein 1 (hHINT1) hydrolyzes the P-N bond to release the 5'-monophosphate. The nucleotide chemical structure consequently impacts the activation pathway efficacy. We report crystal structures of human HINT1 in complex with either the nucleoside GS-441524 or the monophosphate nucleoside GS-441524-MP-both metabolites of remdesivir at 1.30 A and 1.58 A resolution, respectively. Together with enzymatic data, these results disclose the main structural determinants governing activity, namely the steric hindrance of the phosphoramidate moiety as well as ribose modifications altering interactions with Asp43.

Impact of remdesivir modifications on human HINT1 binding - A structural and functional study in the remdesivir activation pathway.,Chazot A, Zimberger C, Fotopoulos I, Canard B, Alvarez K, Ferron F Structure. 2026 May 25:S0969-2126(26)00146-2. doi: 10.1016/j.str.2026.04.015. PMID:42184828<ref>PMID:42184828</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9qtc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ferron F]]
[[Category: Zimberger C]]