2hka: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:2hka.gif|left|200px]] | [[Image:2hka.gif|left|200px]] | ||
'''Crystal structure of bovine NPC2 and cholesterol sulfate complex''' | {{Structure | ||
|PDB= 2hka |SIZE=350|CAPTION= <scene name='initialview01'>2hka</scene>, resolution 1.81Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=C3S:CHOLEST-5-EN-3-YL+HYDROGEN+SULFATE'>C3S</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> | |||
|ACTIVITY= | |||
|GENE= | |||
}} | |||
'''Crystal structure of bovine NPC2 and cholesterol sulfate complex''' | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
2HKA is a [ | 2HKA is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HKA OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/17573352 17573352] | ||
[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| Line 24: | Line 33: | ||
[[Category: beta barrel]] | [[Category: beta barrel]] | ||
''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 17:18:06 2008'' | ||
Revision as of 15:18, 20 March 2008
| |||||||||||||
| 2hka, resolution 1.81Å | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Ligands: | NAG, ACT, SO4, C3S and GOL | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
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 Thu Mar 20 17:18:06 2008
