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| - | [[Image:2hka.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_2hka| PDB=2hka | SCENE= }} | | {{STRUCTURE_2hka| PDB=2hka | SCENE= }} |
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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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| - | ==Overview==
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| - | 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_17573352}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 17573352 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_17573352}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Xu, S.]] | | [[Category: Xu, S.]] |
| | [[Category: Beta barrel]] | | [[Category: Beta barrel]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 06:23:33 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 04:22:35 2008'' |
Revision as of 01:22, 29 July 2008
Template:STRUCTURE 2hka
Crystal structure of bovine NPC2 and cholesterol sulfate complex
Template:ABSTRACT PUBMED 17573352
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 Tue Jul 29 04:22:35 2008
