{"PubmedArticle":{"MedlineCitation":{"@attributes":{"Status":"MEDLINE","Owner":"NLM","IndexingMethod":"Manual"},"PMID":{"@attributes":{"Version":"1"},"@text":"26176916"},"DateCompleted":{"Year":"2016","Month":"04","Day":"28"},"DateRevised":{"Year":"2022","Month":"04","Day":"26"},"Article":{"@attributes":{"PubModel":"Print-Electronic"},"Journal":{"ISSN":{"@attributes":{"IssnType":"Electronic"},"@text":"1476-4687"},"JournalIssue":{"@attributes":{"CitedMedium":"Internet"},"Volume":"526","Issue":"7573","PubDate":{"Year":"2015","Month":"Oct","Day":"15"}},"Title":"Nature","ISOAbbreviation":"Nature"},"ArticleTitle":"Molecular basis of ligand recognition and transport by glucose transporters.","Pagination":{"StartPage":"391","EndPage":"396","MedlinePgn":"391-6"},"ELocationID":[{"@attributes":{"EIdType":"doi","ValidYN":"Y"},"@text":"10.1038\/nature14655"}],"Abstract":{"AbstractText":["The major facilitator superfamily glucose transporters, exemplified by human GLUT1-4, have been central to the study of solute transport. Using lipidic cubic phase crystallization and microfocus X-ray diffraction, we determined the structure of human GLUT3 in complex with D-glucose at 1.5 \u00c5 resolution in an outward-occluded conformation. The high-resolution structure allows discrimination of both \u03b1- and \u03b2-anomers of D-glucose. Two additional structures of GLUT3 bound to the exofacial inhibitor maltose were obtained at 2.6 \u00c5 in the outward-open and 2.4 \u00c5 in the outward-occluded states. In all three structures, the ligands are predominantly coordinated by polar residues from the carboxy terminal domain. Conformational transition from outward-open to outward-occluded entails a prominent local rearrangement of the extracellular part of transmembrane segment TM7. Comparison of the outward-facing GLUT3 structures with the inward-open GLUT1 provides insights into the alternating access cycle for GLUTs, whereby the C-terminal domain provides the primary substrate-binding site and the amino-terminal domain undergoes rigid-body rotation with respect to the C-terminal domain. Our studies provide an important framework for the mechanistic and kinetic understanding of GLUTs and shed light on structure-guided ligand design."]},"AuthorList":{"@attributes":{"CompleteYN":"Y"},"Author":[{"@attributes":{"ValidYN":"Y"},"LastName":"Deng","ForeName":"Dong","Initials":"D","AffiliationInfo":[{"Affiliation":"State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China."},{"Affiliation":"Center for Structural Biology, Tsinghua University, Beijing 100084, China."},{"Affiliation":"Tsinghua-Peking Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Sun","ForeName":"Pengcheng","Initials":"P","AffiliationInfo":[{"Affiliation":"State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China."},{"Affiliation":"Center for Structural Biology, Tsinghua University, Beijing 100084, China."},{"Affiliation":"Tsinghua-Peking Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Yan","ForeName":"Chuangye","Initials":"C","AffiliationInfo":[{"Affiliation":"State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China."},{"Affiliation":"Center for Structural Biology, Tsinghua University, Beijing 100084, China."},{"Affiliation":"Tsinghua-Peking Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Ke","ForeName":"Meng","Initials":"M","AffiliationInfo":[{"Affiliation":"State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China."},{"Affiliation":"Center for Structural Biology, Tsinghua University, Beijing 100084, China."},{"Affiliation":"Tsinghua-Peking Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Jiang","ForeName":"Xin","Initials":"X","AffiliationInfo":[{"Affiliation":"State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China."},{"Affiliation":"Center for Structural Biology, Tsinghua University, Beijing 100084, China."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Xiong","ForeName":"Lei","Initials":"L","AffiliationInfo":[{"Affiliation":"Tsinghua-Peking Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Ren","ForeName":"Wenlin","Initials":"W","AffiliationInfo":[{"Affiliation":"State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China."},{"Affiliation":"Center for Structural Biology, Tsinghua University, Beijing 100084, China."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Hirata","ForeName":"Kunio","Initials":"K","AffiliationInfo":[{"Affiliation":"Advanced Photon Technology Division, Research Infrastructure Group, SR Life Science Instrumentation Unit, RIKEN\/SPring-8 Center, 1-1-1 Kouto Sayo-cho Sayo-gun, Hyogo 679-5148 Japan."},{"Affiliation":"Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Yamamoto","ForeName":"Masaki","Initials":"M","AffiliationInfo":[{"Affiliation":"Advanced Photon Technology Division, Research Infrastructure Group, SR Life Science Instrumentation Unit, RIKEN\/SPring-8 Center, 1-1-1 Kouto Sayo-cho Sayo-gun, Hyogo 679-5148 Japan."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Fan","ForeName":"Shilong","Initials":"S","AffiliationInfo":[{"Affiliation":"Center for Structural Biology, Tsinghua University, Beijing 100084, China."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Yan","ForeName":"Nieng","Initials":"N","AffiliationInfo":[{"Affiliation":"State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China."},{"Affiliation":"Center for Structural Biology, Tsinghua University, Beijing 100084, China."},{"Affiliation":"Tsinghua-Peking Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China."}]}]},"Language":["eng"],"DataBankList":{"@attributes":{"CompleteYN":"Y"},"DataBank":[{"DataBankName":"PDB","AccessionNumberList":{"AccessionNumber":["4ZW9","4ZWB","4ZWC"]}}]},"GrantList":{"@attributes":{"CompleteYN":"Y"},"Grant":[{"Agency":"Howard Hughes Medical Institute","Country":"United States"}]},"PublicationTypeList":{"PublicationType":[{"@attributes":{"UI":"D016428"},"@text":"Journal Article"},{"@attributes":{"UI":"D013485"},"@text":"Research Support, Non-U.S. Gov't"}]},"ArticleDate":[{"@attributes":{"DateType":"Electronic"},"Year":"2015","Month":"07","Day":"15"}]},"MedlineJournalInfo":{"Country":"England","MedlineTA":"Nature","NlmUniqueID":"0410462","ISSNLinking":"0028-0836"},"ChemicalList":{"Chemical":[{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D051272"},"@text":"Glucose Transporter Type 1"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D051274"},"@text":"Glucose Transporter Type 3"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D008024"},"@text":"Ligands"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D011994"},"@text":"Recombinant Proteins"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"C495677"},"@text":"SLC2A1 protein, human"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"C495687"},"@text":"SLC2A3 protein, human"}},{"RegistryNumber":"69-79-4","NameOfSubstance":{"@attributes":{"UI":"D008320"},"@text":"Maltose"}},{"RegistryNumber":"IY9XDZ35W2","NameOfSubstance":{"@attributes":{"UI":"D005947"},"@text":"Glucose"}}]},"CitationSubset":["IM"],"MeshHeadingList":{"MeshHeading":[{"DescriptorName":{"@attributes":{"UI":"D001665","MajorTopicYN":"N"},"@text":"Binding Sites"}},{"DescriptorName":{"@attributes":{"UI":"D001692","MajorTopicYN":"N"},"@text":"Biological Transport"}},{"DescriptorName":{"@attributes":{"UI":"D002462","MajorTopicYN":"N"},"@text":"Cell Membrane"},"QualifierName":[{"@attributes":{"UI":"Q000378","MajorTopicYN":"N"},"@text":"metabolism"}]},{"DescriptorName":{"@attributes":{"UI":"D018360","MajorTopicYN":"N"},"@text":"Crystallography, X-Ray"}},{"DescriptorName":{"@attributes":{"UI":"D005947","MajorTopicYN":"N"},"@text":"Glucose"},"QualifierName":[{"@attributes":{"UI":"Q000737","MajorTopicYN":"Y"},"@text":"chemistry"},{"@attributes":{"UI":"Q000378","MajorTopicYN":"Y"},"@text":"metabolism"}]},{"DescriptorName":{"@attributes":{"UI":"D051272","MajorTopicYN":"N"},"@text":"Glucose Transporter Type 1"},"QualifierName":[{"@attributes":{"UI":"Q000737","MajorTopicYN":"N"},"@text":"chemistry"},{"@attributes":{"UI":"Q000378","MajorTopicYN":"N"},"@text":"metabolism"}]},{"DescriptorName":{"@attributes":{"UI":"D051274","MajorTopicYN":"N"},"@text":"Glucose Transporter Type 3"},"QualifierName":[{"@attributes":{"UI":"Q000737","MajorTopicYN":"Y"},"@text":"chemistry"},{"@attributes":{"UI":"Q000378","MajorTopicYN":"Y"},"@text":"metabolism"}]},{"DescriptorName":{"@attributes":{"UI":"D006801","MajorTopicYN":"N"},"@text":"Humans"}},{"DescriptorName":{"@attributes":{"UI":"D007700","MajorTopicYN":"N"},"@text":"Kinetics"}},{"DescriptorName":{"@attributes":{"UI":"D008024","MajorTopicYN":"N"},"@text":"Ligands"}},{"DescriptorName":{"@attributes":{"UI":"D008320","MajorTopicYN":"N"},"@text":"Maltose"},"QualifierName":[{"@attributes":{"UI":"Q000737","MajorTopicYN":"N"},"@text":"chemistry"},{"@attributes":{"UI":"Q000378","MajorTopicYN":"N"},"@text":"metabolism"}]},{"DescriptorName":{"@attributes":{"UI":"D008958","MajorTopicYN":"N"},"@text":"Models, Molecular"}},{"DescriptorName":{"@attributes":{"UI":"D011485","MajorTopicYN":"N"},"@text":"Protein Binding"}},{"DescriptorName":{"@attributes":{"UI":"D011487","MajorTopicYN":"N"},"@text":"Protein Conformation"}},{"DescriptorName":{"@attributes":{"UI":"D011994","MajorTopicYN":"N"},"@text":"Recombinant Proteins"},"QualifierName":[{"@attributes":{"UI":"Q000737","MajorTopicYN":"N"},"@text":"chemistry"},{"@attributes":{"UI":"Q000378","MajorTopicYN":"N"},"@text":"metabolism"}]},{"DescriptorName":{"@attributes":{"UI":"D012399","MajorTopicYN":"N"},"@text":"Rotation"}},{"DescriptorName":{"@attributes":{"UI":"D013329","MajorTopicYN":"N"},"@text":"Structure-Activity Relationship"}}]}},"PubmedData":{"History":{"PubMedPubDate":[{"@attributes":{"PubStatus":"received"},"Year":"2015","Month":"1","Day":"6"},{"@attributes":{"PubStatus":"accepted"},"Year":"2015","Month":"6","Day":"12"},{"@attributes":{"PubStatus":"entrez"},"Year":"2015","Month":"7","Day":"16","Hour":"6","Minute":"0"},{"@attributes":{"PubStatus":"pubmed"},"Year":"2015","Month":"7","Day":"16","Hour":"6","Minute":"0"},{"@attributes":{"PubStatus":"medline"},"Year":"2016","Month":"4","Day":"29","Hour":"6","Minute":"0"}]},"PublicationStatus":"ppublish","ArticleIdList":{"ArticleId":[{"@attributes":{"IdType":"pubmed"},"@text":"26176916"},{"@attributes":{"IdType":"doi"},"@text":"10.1038\/nature14655"},{"@attributes":{"IdType":"pii"},"@text":"nature14655"}]}}}}