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Structural basis for molecular recognition of folic acid by folate receptors
文献类型：期刊论文
| 作者 | Chen, Chen4,5; Ke, Jiyuan5; Zhou, X. Edward5; Yi, Wei1; Brunzelle, Joseph S.2; Li, Jun3 ; Yong, Eu-Leong3; Xu, H. Eric1,5; Melcher, Karsten5
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| 刊名 | NATURE
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| 出版日期 | 2013-08-22 |
| 卷号 | 500期号:7463页码:486-+ |
| ISSN号 | 0028-0836 |
| DOI | 10.1038/nature12327 |
| 文献子类 | Article |
| 英文摘要 | Folate receptors (FR alpha, FR beta and FR gamma) are cysteine-rich cell-surface glycoproteins that bind folate with high affinity to mediate cellular uptake of folate. Although expressed at very low levels in most tissues, folate receptors, especially FR alpha, are expressed at high levels in numerous cancers to meet the folate demand of rapidly dividing cells under low folate conditions(1-3). The folate dependency of many tumours has been therapeutically and diagnostically exploited by administration of anti-FR alpha antibodies, high-affinity antifolates(4,5), folate-based imaging agents and folate-conjugated drugs and toxins(6-8). To understand how folate binds its receptors, we determined the crystal structure of human FR alpha in complex with folic acid at 2.8 angstrom resolution. FR alpha has a globular structure stabilized by eight disulphide bonds and contains a deep open folate-binding pocket comprised of residues that are conserved in all receptor subtypes. The folate pteroate moiety is buried inside the receptor, whereas its glutamate moiety is solvent-exposed and sticks out of the pocket entrance, allowing it to be conjugated to drugs without adversely affecting FR alpha binding. The extensive interactions between the receptor and ligand readily explain the high folate-binding affinity of folate receptors and provide a template for designing more specific drugs targeting the folate receptor system. |
| WOS关键词 | DIFFRACTION ; CONJUGATE ; CHEMISTRY ; TISSUES ; CELLS |
| 资助项目 | Michigan Economic Development Corporation[00000000] ; Michigan Technology Tri-Corridor[085P1000817] ; Office of Science of the US Department of Energy[DE-AC02-06CH11357] ; Jay and Betty Van Andel Foundation[00000000] ; American Asthma Foundation[00000000] ; Ministry of Science and Technology (China)[2012ZX09301001-005] ; Ministry of Science and Technology (China)[2012CB910403] ; Amway (China)[00000000] ; National Institutes of Health[R01 DK071662] ; National Institutes of Health[R01 GM102545] ; National Research Foundation Singapore[NMRC/CSA/026/2011] ; NUS Graduate School for Integrative Sciences and Engineering Scholarship[00000000] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| 出版者 | NATURE PUBLISHING GROUP |
| WOS记录号 | WOS:000323316100041 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277498]  |
| 专题 | 药物靶标结构与功能中心 |
| 通讯作者 | Yong, Eu-Leong |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, VARI SIMM Ctr,Ctr Struct & Funct Drug Targets, Shanghai 201203, Peoples R China; 2.Northwestern Univ, Synchrotron Res Ctr, Life Sci Collaborat Access Team, Argonne, IL 60439 USA; 3.Natl Univ Singapore, Yong Loo Lin Sch Med, Natl Univ Hosp, Dept Obstet & Gynecol, Singapore 119074, Singapore 4.Natl Univ Singapore, Grad Sch Integrat Sci & Engn, Singapore 117456, Singapore; 5.Van Andel Res Inst, Program Struct Biol & Drug Discovery, Grand Rapids, MI 49503 USA; |
| 推荐引用方式 GB/T 7714 | Chen, Chen,Ke, Jiyuan,Zhou, X. Edward,et al. Structural basis for molecular recognition of folic acid by folate receptors[J]. NATURE,2013,500(7463):486-+. |
| APA | Chen, Chen.,Ke, Jiyuan.,Zhou, X. Edward.,Yi, Wei.,Brunzelle, Joseph S..,...&Melcher, Karsten.(2013).Structural basis for molecular recognition of folic acid by folate receptors.NATURE,500(7463),486-+. |
| MLA | Chen, Chen,et al."Structural basis for molecular recognition of folic acid by folate receptors".NATURE 500.7463(2013):486-+. |
入库方式： OAI收割
来源：上海药物研究所
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