4lrh: Difference between revisions
New page: {{STRUCTURE_4lrh| PDB=4lrh | SCENE= }} ===Crystal structure of human folate receptor alpha in complex with folic acid=== {{ABSTRACT_PUBMED_23851396}} ==Disease== [[http://www.uniprot... |
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== | ==Crystal structure of human folate receptor alpha in complex with folic acid== | ||
[[http://www.uniprot.org/uniprot/FOLR1_HUMAN FOLR1_HUMAN | <StructureSection load='4lrh' size='340' side='right'caption='[[4lrh]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4lrh]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4keo 4keo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LRH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LRH FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FOL:FOLIC+ACID'>FOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4lrh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lrh OCA], [https://pdbe.org/4lrh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lrh RCSB], [https://www.ebi.ac.uk/pdbsum/4lrh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lrh ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/FOLR1_HUMAN FOLR1_HUMAN] Neurodegenerative syndrome due to cerebral folate transport deficiency. Neurodegeneration due to cerebral folate transport deficiency (NCFTD) [MIM:[https://omim.org/entry/613068 613068]: A neurodegenerative disorder resulting from brain-specific folate deficiency early in life. Onset is apparent in late infancy with severe developmental regression, movement disturbances, epilepsy and leukodystrophy. Note=The disease is caused by mutations affecting the gene represented in this entry. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/FOLR1_HUMAN FOLR1_HUMAN] Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate to the interior of cells. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Folate receptors (FRalpha, FRbeta and FRgamma) 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 FRalpha, are expressed at high levels in numerous cancers to meet the folate demand of rapidly dividing cells under low folate conditions. The folate dependency of many tumours has been therapeutically and diagnostically exploited by administration of anti-FRalpha antibodies, high-affinity antifolates, folate-based imaging agents and folate-conjugated drugs and toxins. To understand how folate binds its receptors, we determined the crystal structure of human FRalpha in complex with folic acid at 2.8 A resolution. FRalpha 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 FRalpha 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. | |||
Structural basis for molecular recognition of folic acid by folate receptors.,Chen C, Ke J, Zhou XE, Yi W, Brunzelle JS, Li J, Yong EL, Xu HE, Melcher K Nature. 2013 Jul 14. doi: 10.1038/nature12327. PMID:23851396<ref>PMID:23851396</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4lrh" style="background-color:#fffaf0;"></div> | |||
== | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Brunzelle | [[Category: Large Structures]] | ||
[[Category: Chen | [[Category: Brunzelle JS]] | ||
[[Category: Ke | [[Category: Chen C]] | ||
[[Category: Li | [[Category: Ke J]] | ||
[[Category: Melcher | [[Category: Li J]] | ||
[[Category: Xu | [[Category: Melcher K]] | ||
[[Category: Yi | [[Category: Xu HE]] | ||
[[Category: Young | [[Category: Yi W]] | ||
[[Category: Zhou | [[Category: Young E-L]] | ||
[[Category: Zhou XE]] | |||
Latest revision as of 14:22, 14 December 2022
Crystal structure of human folate receptor alpha in complex with folic acidCrystal structure of human folate receptor alpha in complex with folic acid
Structural highlights
DiseaseFOLR1_HUMAN Neurodegenerative syndrome due to cerebral folate transport deficiency. Neurodegeneration due to cerebral folate transport deficiency (NCFTD) [MIM:613068: A neurodegenerative disorder resulting from brain-specific folate deficiency early in life. Onset is apparent in late infancy with severe developmental regression, movement disturbances, epilepsy and leukodystrophy. Note=The disease is caused by mutations affecting the gene represented in this entry. FunctionFOLR1_HUMAN Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate to the interior of cells. Publication Abstract from PubMedFolate receptors (FRalpha, FRbeta and FRgamma) 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 FRalpha, are expressed at high levels in numerous cancers to meet the folate demand of rapidly dividing cells under low folate conditions. The folate dependency of many tumours has been therapeutically and diagnostically exploited by administration of anti-FRalpha antibodies, high-affinity antifolates, folate-based imaging agents and folate-conjugated drugs and toxins. To understand how folate binds its receptors, we determined the crystal structure of human FRalpha in complex with folic acid at 2.8 A resolution. FRalpha 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 FRalpha 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. Structural basis for molecular recognition of folic acid by folate receptors.,Chen C, Ke J, Zhou XE, Yi W, Brunzelle JS, Li J, Yong EL, Xu HE, Melcher K Nature. 2013 Jul 14. doi: 10.1038/nature12327. PMID:23851396[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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