1r5l
From Proteopedia
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| - | [[Image:1r5l.jpg|left|200px]] | + | [[Image:1r5l.jpg|left|200px]] |
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| - | '''Crystal Structure of Human Alpha-Tocopherol Transfer Protein Bound to its Ligand''' | + | {{Structure |
| + | |PDB= 1r5l |SIZE=350|CAPTION= <scene name='initialview01'>1r5l</scene>, resolution 1.50Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=VIV:(2R)-2,5,7,8-TETRAMETHYL-2-[(4R,8R)-4,8,12-TRIMETHYLTRIDECYL]CHROMAN-6-OL'>VIV</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= TTPA OR TPP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal Structure of Human Alpha-Tocopherol Transfer Protein Bound to its Ligand''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==Disease== | ==Disease== | ||
| - | Known | + | Known diseases associated with this structure: Ataxia with isolated vitamin E deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600415 600415]], Ceroid-lipofuscinosis, neuronal 2, classic late infantile OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607998 607998]] |
==About this Structure== | ==About this Structure== | ||
| - | 1R5L is a [ | + | 1R5L is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R5L OCA]. |
==Reference== | ==Reference== | ||
| - | Crystal structure of human alpha-tocopherol transfer protein bound to its ligand: implications for ataxia with vitamin E deficiency., Min KC, Kovall RA, Hendrickson WA, Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14713-8. Epub 2003 Dec 1. PMID:[http:// | + | Crystal structure of human alpha-tocopherol transfer protein bound to its ligand: implications for ataxia with vitamin E deficiency., Min KC, Kovall RA, Hendrickson WA, Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14713-8. Epub 2003 Dec 1. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14657365 14657365] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: tocopherol]] | [[Category: tocopherol]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:47:10 2008'' |
Revision as of 11:47, 20 March 2008
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| , resolution 1.50Å | |||||||
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| Ligands: | |||||||
| Gene: | TTPA OR TPP1 (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of Human Alpha-Tocopherol Transfer Protein Bound to its Ligand
Contents |
Overview
Human alpha-tocopherol (alpha-T) transfer protein (ATTP) plays a central role in vitamin E homeostasis, preventing degradation of alpha-T by routing this lipophilic molecule for secretion by hepatocytes. Mutations in the gene encoding ATTP have been shown to cause a severe deficiency in alpha-T, which results in a progressive neurodegenerative spinocerebellar ataxia, known as ataxia with vitamin E deficiency (AVED). We have determined the high-resolution crystal structure of human ATTP with (2R,4'R,8'R)-alpha-T in the binding pocket. Surprisingly, the ligand is sequestered deep in the hydrophobic core of the protein, implicating a large structural rearrangement for the entry and release of alpha-T. A comparison to the structure of a related protein, Sec14p, crystallized without a bona fide ligand, shows a possibly relevant open conformation for this family of proteins. Furthermore, of the known mutations that cause AVED, one mutation, L183P, is located directly in the binding pocket. Finally, three mutations associated with AVED involve arginine residues that are grouped together on the surface of ATTP. We propose that this positively charged surface may serve to orient an interacting protein, which might function to regulate the release of alpha-T through an induced change in conformation of ATTP.
Disease
Known diseases associated with this structure: Ataxia with isolated vitamin E deficiency OMIM:[600415], Ceroid-lipofuscinosis, neuronal 2, classic late infantile OMIM:[607998]
About this Structure
1R5L is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of human alpha-tocopherol transfer protein bound to its ligand: implications for ataxia with vitamin E deficiency., Min KC, Kovall RA, Hendrickson WA, Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14713-8. Epub 2003 Dec 1. PMID:14657365
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