{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1363670319293558656.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1002/prot.20015"}},{"identifier":{"@type":"URI","@value":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fprot.20015"}},{"identifier":{"@type":"URI","@value":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/prot.20015"}}],"dc:title":[{"@value":"Ultrahigh resolution drug design I: Details of interactions in human aldose reductase–inhibitor complex at 0.66 Å"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title><jats:p>The first subatomic resolution structure of a 36 kDa protein [aldose reductase (AR)] is presented. AR was cocrystallized at pH 5.0 with its cofactor NADP<jats:sup>+</jats:sup> and inhibitor IDD 594, a therapeutic candidate for the treatment of diabetic complications. X‐ray diffraction data were collected up to 0.62 Å resolution and treated up to 0.66 Å resolution. Anisotropic refinement followed by a blocked matrix inversion produced low standard deviations (<0.005 Å). The model was very well ordered overall (CA atoms' mean B factor is 5.5 Å<jats:sup>2</jats:sup>). The model and the electron‐density maps revealed fine features, such as H‐atoms, bond densities, and significant deviations from standard stereochemistry. Other features, such as networks of hydrogen bonds (H bonds), a large number of multiple conformations, and solvent structure were also better defined. Most of the atoms in the active site region were extremely well ordered (mean B ∼3 Å<jats:sup>2</jats:sup>), leading to the identification of the protonation states of the residues involved in catalysis. The electrostatic interactions of the inhibitor's charged carboxylate head with the catalytic residues and the charged coenzyme NADP<jats:sup>+</jats:sup> explained the inhibitor's noncompetitive character. Furthermore, a short contact involving the IDD 594 bromine atom explained the selectivity profile of the inhibitor, important feature to avoid toxic effects. The presented structure and the details revealed are instrumental for better understanding of the inhibition mechanism of AR by IDD 594, and hence, for the rational drug design of future inhibitors. This work demonstrates the capabilities of subatomic resolution experiments and stimulates further developments of methods allowing the use of the full potential of these experiments. Proteins 2004. © 2004 Wiley‐Liss, Inc.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1383670319293558656","@type":"Researcher","foaf:name":[{"@value":"E.I. Howard"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319293558530","@type":"Researcher","foaf:name":[{"@value":"R. Sanishvili"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319293558661","@type":"Researcher","foaf:name":[{"@value":"R.E. Cachau"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319293558531","@type":"Researcher","foaf:name":[{"@value":"A. Mitschler"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319293558662","@type":"Researcher","foaf:name":[{"@value":"B. Chevrier"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319293558657","@type":"Researcher","foaf:name":[{"@value":"P. Barth"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319293558529","@type":"Researcher","foaf:name":[{"@value":"V. Lamour"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319293558660","@type":"Researcher","foaf:name":[{"@value":"M. Van Zandt"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319293558658","@type":"Researcher","foaf:name":[{"@value":"E. Sibley"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319293558532","@type":"Researcher","foaf:name":[{"@value":"C. Bon"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319293558534","@type":"Researcher","foaf:name":[{"@value":"D. Moras"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319293558528","@type":"Researcher","foaf:name":[{"@value":"T.R. Schneider"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319293558659","@type":"Researcher","foaf:name":[{"@value":"A. Joachimiak"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670319293558533","@type":"Researcher","foaf:name":[{"@value":"A. Podjarny"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"08873585"},{"@type":"EISSN","@value":"10970134"}],"prism:publicationName":[{"@value":"Proteins: Structure, Function, and Bioinformatics"}],"dc:publisher":[{"@value":"Wiley"}],"prism:publicationDate":"2004-04-02","prism:volume":"55","prism:number":"4","prism:startingPage":"792","prism:endingPage":"804"},"reviewed":"false","dc:rights":["http://onlinelibrary.wiley.com/termsAndConditions#vor"],"url":[{"@id":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fprot.20015"},{"@id":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/prot.20015"}],"createdAt":"2004-04-02","modifiedAt":"2023-10-13","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050001202113892096","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"High-resolution structure of the recombinant sweet-tasting protein thaumatin I."}]},{"@id":"https://cir.nii.ac.jp/crid/1050306506455413888","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Control of a two-dimensional molecular structure by cooperative halogen and hydrogen bonds"}]},{"@id":"https://cir.nii.ac.jp/crid/1360021389796825984","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Site‐specific relaxation of peptide bond planarity induced by electrically attracted proton/deuteron observed by neutron crystallography"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285710049765504","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"High-resolution X-ray crystal structure of bovine H-protein using the high-pressure cryocooling method"}]},{"@id":"https://cir.nii.ac.jp/crid/1360286992010952576","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"A molecular interaction field describing nonconventional intermolecular interactions and its application to protein–ligand interaction prediction"}]},{"@id":"https://cir.nii.ac.jp/crid/1360302864788387712","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Subatomic structure of orthorhombic thaumatin at 0.89 Å reveals that highly flexible conformations are crucial for thaumatin sweetness"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567183073315456","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Antioxidative Pseudoenzymatic Mechanism of NAD(P)H Coexisting with Oxyhemoglobin for Suppressed Methemoglobin Formation"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1002/prot.20015"},{"@type":"CROSSREF","@value":"10.1002/pro.4765_references_DOI_Y2Zi85HCs8owG6RYIcruSEK2WWp"},{"@type":"CROSSREF","@value":"10.1107/s174430911101373x_references_DOI_Y2Zi85HCs8owG6RYIcruSEK2WWp"},{"@type":"CROSSREF","@value":"10.1107/s090904951302373x_references_DOI_Y2Zi85HCs8owG6RYIcruSEK2WWp"},{"@type":"CROSSREF","@value":"10.1016/j.bbrc.2024.149601_references_DOI_Y2Zi85HCs8owG6RYIcruSEK2WWp"},{"@type":"CROSSREF","@value":"10.1021/acs.biochem.8b01314_references_DOI_Y2Zi85HCs8owG6RYIcruSEK2WWp"},{"@type":"CROSSREF","@value":"10.1039/c4ra10235e_references_DOI_Y2Zi85HCs8owG6RYIcruSEK2WWp"},{"@type":"CROSSREF","@value":"10.1016/j.jmgm.2019.107515_references_DOI_Y2Zi85HCs8owG6RYIcruSEK2WWp"}]}