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Of its three domains\u2014N\u2010terminal, middle, and C\u2010terminal\u2014the N\u2010terminal domain (NTD) plays a role in ATP hydrolysis, which is required for the chaperone function of Hsp90 in vivo. Precise information about ATP (and ADP) recognition is useful for designing drugs that target the ATP\u2010binding site. X\u2010ray crystal structures of human Hsp90\u03b1\u2010NTD have revealed hydrogen bonds around the ADP\u2010binding site, but the exact hydrogen\u2010bond patterns are unclear, mainly because their structures lack the hydrogen atoms essential for identifying donor and acceptor pairs. Here, we performed neutron structural analyses of human Hsp90\u03b1\u2010NTD in both its apo and ADP\u2010bound forms. These structures clarify the hydrogen bonds, including the orientations of water molecules. The neutron structures show that ADP and magnesium binding do not perturb the apo state hydrogen\u2010bond network. The orientation of a water molecule and the position of the Met98 side chain indicate that lone pair\u2013\u03c0 and CH\u2013\u03c0 interactions stabilize the binding of the adenine ring. A Hsp90\u2010specific intramolecular hydrogen bond between the ribose moiety and the phosphate implies its contribution to the ATP hydrolysis catalyzed by Hsp90. The precise view of the ADP\u2010binding site indicates that the unperturbed hydration structure plays an important role in ADP recognition.<\/jats:p>","DOI":"10.1002\/pro.70619","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T12:56:34Z","timestamp":1779108994000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unperturbed hydration structure involves\n                    <scp>ADP<\/scp>\n                    recognition in the N\u2010terminal domain of human heat shock protein 90\u03b1"],"prefix":"10.1002","volume":"35","author":[{"given":"Yu","family":"Hirano","sequence":"first","affiliation":[{"name":"Institute for Quantum Life Science National Institutes for Quantum Science and Technology  Chiba Japan"},{"name":"Center of Quantum Life Science for Structural Therapeutics Chiba University  Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuhiro","family":"Kusaka","sequence":"additional","affiliation":[{"name":"Neutron Industrial Application Promotion Center Comprehensive Research Organization for Science and Society  Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toyoyuki","family":"Ose","sequence":"additional","affiliation":[{"name":"Faculty of Advanced Life Science Hokkaido University  Sapporo Japan"},{"name":"Faculty of Pharmaceutical Sciences Hokkaido University  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Kurihara","sequence":"additional","affiliation":[{"name":"Institute for Quantum Life Science National Institutes for Quantum Science and Technology  Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Aburai","sequence":"additional","affiliation":[{"name":"Research Division Kyowa Kirin Co. 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