2hka

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[[Image:2hka.gif|left|200px]]
[[Image:2hka.gif|left|200px]]
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{{Structure
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The line below this paragraph, containing "STRUCTURE_2hka", creates the "Structure Box" on the page.
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|LIGAND= <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=C3S:CHOLEST-5-EN-3-YL+HYDROGEN+SULFATE'>C3S</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
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{{STRUCTURE_2hka| PDB=2hka | SCENE= }}
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2hka FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hka OCA], [http://www.ebi.ac.uk/pdbsum/2hka PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2hka RCSB]</span>
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'''Crystal structure of bovine NPC2 and cholesterol sulfate complex'''
'''Crystal structure of bovine NPC2 and cholesterol sulfate complex'''
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[[Category: Stock, A M.]]
[[Category: Stock, A M.]]
[[Category: Xu, S.]]
[[Category: Xu, S.]]
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[[Category: beta barrel]]
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[[Category: Beta barrel]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 06:23:33 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:31:34 2008''
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Revision as of 03:23, 4 May 2008

Image:2hka.gif

Template:STRUCTURE 2hka

Crystal structure of bovine NPC2 and cholesterol sulfate complex


Overview

NPC2 is a small lysosomal glycoprotein that binds cholesterol with submicromolar affinity. Deficiency in NPC2 is the cause of Niemann-Pick type C2 disease, a fatal neurovisceral disorder characterized by accumulation of cholesterol in lysosomes. Here we report the crystal structure of bovine NPC2 bound to cholesterol-3-O-sulfate, an analog that binds with greater apparent affinity than cholesterol. Structures of both apo-bound and sterol-bound NPC2 were observed within the same crystal lattice, with an asymmetric unit containing one molecule of apoNPC2 and two molecules of sterol-bound NPC2. As predicted from a previously determined structure of apoNPC2, the sterol binds in a deep hydrophobic pocket sandwiched between the two beta-sheets of NPC2, with only the sulfate substituent of the ligand exposed to solvent. In the two available structures of apoNPC2, the incipient ligand-binding pocket, which ranges from a loosely packed hydrophobic core to a small tunnel, is too small to accommodate cholesterol. In the presence of sterol, the pocket expands, facilitated by a slight separation of the beta-strands and substantial reorientation of some side chains, resulting in a perfect molding of the pocket around the hydrocarbon portion of cholesterol. A notable feature is the repositioning of two aromatic residues at the tunnel entrance that are essential for NPC2 function. The NPC2 structures provide evidence of a malleable binding site, consistent with the previously documented broad range of sterol ligand specificity.

About this Structure

2HKA is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.

Reference

Structural basis of sterol binding by NPC2, a lysosomal protein deficient in Niemann-Pick type C2 disease., Xu S, Benoff B, Liou HL, Lobel P, Stock AM, J Biol Chem. 2007 Aug 10;282(32):23525-31. Epub 2007 Jun 14. PMID:17573352 Page seeded by OCA on Sun May 4 06:23:33 2008

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