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==Crystal Structure of D48V mutant of Human Glycolipid Transfer Protein complexed with 3-O-sulfo galactosylceramide containing nervonoyl acyl chain==
==Crystal Structure of D48V mutant of Human Glycolipid Transfer Protein complexed with 3-O-sulfo galactosylceramide containing nervonoyl acyl chain==
<StructureSection load='3s0i' size='340' side='right' caption='[[3s0i]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
<StructureSection load='3s0i' size='340' side='right'caption='[[3s0i]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3s0i]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3S0I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3S0I FirstGlance]. <br>
<table><tr><td colspan='2'>[[3s0i]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3S0I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3S0I FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIS:(15Z)-N-((1S,2R,3E)-2-HYDROXY-1-{[(3-O-SULFO-BETA-D-GALACTOPYRANOSYL)OXY]METHYL}HEPTADEC-3-ENYL)TETRACOS-15-ENAMIDE'>CIS</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2evt|2evt]], [[3rzn|3rzn]], [[3ric|3ric]], [[3rwv|3rwv]], [[3s0k|3s0k]], [[1swx|1swx]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIS:(15Z)-N-((1S,2R,3E)-2-HYDROXY-1-{[(3-O-SULFO-BETA-D-GALACTOPYRANOSYL)OXY]METHYL}HEPTADEC-3-ENYL)TETRACOS-15-ENAMIDE'>CIS</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GLTP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3s0i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s0i OCA], [https://pdbe.org/3s0i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3s0i RCSB], [https://www.ebi.ac.uk/pdbsum/3s0i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3s0i ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3s0i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s0i OCA], [http://pdbe.org/3s0i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3s0i RCSB], [http://www.ebi.ac.uk/pdbsum/3s0i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3s0i ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/GLTP_HUMAN GLTP_HUMAN]] Accelerates the intermembrane transfer of various glycolipids. Catalyzes the transfer of various glycosphingolipids between membranes but does not catalyze the transfer of phospholipids. May be involved in the intracellular translocation of glucosylceramides.<ref>PMID:18261224</ref> <ref>PMID:15504043</ref> <ref>PMID:17980653</ref> <ref>PMID:15329726</ref> 
[https://www.uniprot.org/uniprot/GLTP_HUMAN GLTP_HUMAN] Accelerates the intermembrane transfer of various glycolipids. Catalyzes the transfer of various glycosphingolipids between membranes but does not catalyze the transfer of phospholipids. May be involved in the intracellular translocation of glucosylceramides.<ref>PMID:18261224</ref> <ref>PMID:15504043</ref> <ref>PMID:17980653</ref> <ref>PMID:15329726</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human glycolipid transfer protein (GLTP) fold represents a novel structural motif for lipid binding/transfer and reversible membrane translocation. GLTPs transfer glycosphingolipids (GSLs) that are key regulators of cell growth, division, surface adhesion, and neurodevelopment. Herein, we report structure-guided engineering of the lipid binding features of GLTP. New crystal structures of wild-type GLTP and two mutants (D48V and A47D ||D48V), each containing bound N-nervonoyl-sulfatide, reveal the molecular basis for selective anchoring of sulfatide (3-O-sulfo-galactosylceramide) by D48V-GLTP. Directed point mutations of "portal entrance" residues, A47 and D48, reversibly regulate sphingosine access to the hydrophobic pocket via a mechanism that could involve homodimerization. "Door-opening" conformational changes by phenylalanines within the hydrophobic pocket are revealed during lipid encapsulation by new crystal structures of bona fide apo-GLTP and GLTP complexed with N-oleoyl-glucosylceramide. The development of "engineered GLTPs" with enhanced specificity for select GSLs provides a potential new therapeutic approach for targeting GSL-mediated pathologies.
 
Enhanced selectivity for sulfatide by engineered human glycolipid transfer protein.,Samygina VR, Popov AN, Cabo-Bilbao A, Ochoa-Lizarralde B, Goni-de-Cerio F, Zhai X, Molotkovsky JG, Patel DJ, Brown RE, Malinina L Structure. 2011 Nov 9;19(11):1644-54. PMID:22078563<ref>PMID:22078563</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3s0i" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Brown, R E]]
[[Category: Large Structures]]
[[Category: Cabo-Bilbao, A]]
[[Category: Brown RE]]
[[Category: Malinina, L]]
[[Category: Cabo-Bilbao A]]
[[Category: Ochoa-Lizarralde, B]]
[[Category: Malinina L]]
[[Category: Patel, D J]]
[[Category: Ochoa-Lizarralde B]]
[[Category: Popov, A N]]
[[Category: Patel DJ]]
[[Category: Samygina, V]]
[[Category: Popov AN]]
[[Category: Gltp-fold]]
[[Category: Samygina V]]
[[Category: Lipid transport]]
[[Category: Transport]]

Latest revision as of 12:42, 14 March 2024

Crystal Structure of D48V mutant of Human Glycolipid Transfer Protein complexed with 3-O-sulfo galactosylceramide containing nervonoyl acyl chain

3s0i, resolution 1.50Å

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