1g13
From Proteopedia
(New page: 200px<br /> <applet load="1g13" size="450" color="white" frame="true" align="right" spinBox="true" caption="1g13, resolution 2.0Å" /> '''HUMAN GM2 ACTIVATOR ...) |
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| - | [[Image:1g13.gif|left|200px]]<br /> | + | [[Image:1g13.gif|left|200px]]<br /><applet load="1g13" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1g13" size=" | + | |
caption="1g13, resolution 2.0Å" /> | caption="1g13, resolution 2.0Å" /> | ||
'''HUMAN GM2 ACTIVATOR STRUCTURE'''<br /> | '''HUMAN GM2 ACTIVATOR STRUCTURE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | GM2 activator protein (GM2-AP) belongs to a small group of non- enzymatic | + | GM2 activator protein (GM2-AP) belongs to a small group of non- enzymatic lysosomal proteins that act as cofactors in the sequential degradation of gangliosides. It has been postulated that GM2-AP extracts single GM2 molecules from membranes and presents them in soluble form to beta-hexosaminidase A for cleavage of N-acetyl-d-galactosamine and conversion to GM3. The high affinity of GM2-AP for GM2 is based on specfic recognition of the oligosaccharide moiety as well as the ceramide lipid tail. Genetic defects in GM2-AP result in an atypical form of Tay-Sachs disease known as variant AB GM2 gangliosidosis. The 2.0 A resolution crystal structure of GM2-AP reported here reveals a previously unobserved fold whose main feature is an eight-stranded cup-shaped anti-parallel beta-pleated sheet. The striking feature of the GM2-AP structure is that it possesses an accessible central hydrophobic cavity rather than a buried hydrophobic core. The dimensions of this cavity (12 Ax14 Ax22 A) are suitable for binding 18-carbon lipid acyl chains. Flexible surface loops and a short alpha-helix decorate the mouth of the beta-cup and may control lipid entry to the cavity. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1G13 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with EPE as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1G13 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=EPE:'>EPE</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G13 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Li, S | + | [[Category: Li, S C.]] |
[[Category: Rastinejad, F.]] | [[Category: Rastinejad, F.]] | ||
| - | [[Category: Wright, C | + | [[Category: Wright, C S.]] |
[[Category: EPE]] | [[Category: EPE]] | ||
[[Category: beta cup]] | [[Category: beta cup]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:44:59 2008'' |
Revision as of 10:45, 21 February 2008
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HUMAN GM2 ACTIVATOR STRUCTURE
Contents |
Overview
GM2 activator protein (GM2-AP) belongs to a small group of non- enzymatic lysosomal proteins that act as cofactors in the sequential degradation of gangliosides. It has been postulated that GM2-AP extracts single GM2 molecules from membranes and presents them in soluble form to beta-hexosaminidase A for cleavage of N-acetyl-d-galactosamine and conversion to GM3. The high affinity of GM2-AP for GM2 is based on specfic recognition of the oligosaccharide moiety as well as the ceramide lipid tail. Genetic defects in GM2-AP result in an atypical form of Tay-Sachs disease known as variant AB GM2 gangliosidosis. The 2.0 A resolution crystal structure of GM2-AP reported here reveals a previously unobserved fold whose main feature is an eight-stranded cup-shaped anti-parallel beta-pleated sheet. The striking feature of the GM2-AP structure is that it possesses an accessible central hydrophobic cavity rather than a buried hydrophobic core. The dimensions of this cavity (12 Ax14 Ax22 A) are suitable for binding 18-carbon lipid acyl chains. Flexible surface loops and a short alpha-helix decorate the mouth of the beta-cup and may control lipid entry to the cavity.
Disease
Known disease associated with this structure: GM2-gangliosidosis, AB variant OMIM:[272750]
About this Structure
1G13 is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structure of human GM2-activator protein with a novel beta-cup topology., Wright CS, Li SC, Rastinejad F, J Mol Biol. 2000 Dec 1;304(3):411-22. PMID:11090283
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