9QRO

HINT1 complexed with GS-441524-MP

Summary for 9QRO

• Entry DOI: 10.2210/pdb9qro/pdb
• Descriptor: Histidine triad nucleotide-binding protein 1, [(2~{R},3~{S},4~{R},5~{R})-5-(4-azanylpyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-bis(oxidanyl)oxolan-2-yl]methyl dihydrogen phosphate, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (4 entities in total)
• Functional Keywords: complex, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 28214.34

Authors

Zimberger, C.,Ferron, F. (deposition date: 2025-04-04, release date: 2026-06-03)

Primary citation

Chazot, A.,Zimberger, C.,Fotopoulos, I.,Canard, B.,Alvarez, K.,Ferron, F.
Impact of remdesivir modifications on human HINT1 binding - A structural and functional study in the remdesivir activation pathway.
Structure, 2026

PubMed Abstract: 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 Å and 1.58 Å 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.

PubMed: 42184828
DOI: 10.1016/j.str.2026.04.015

Experimental method

X-RAY DIFFRACTION (1.58 Å)