2hka
From Proteopedia
(New page: 200px<br /><applet load="2hka" size="450" color="white" frame="true" align="right" spinBox="true" caption="2hka, resolution 1.81Å" /> '''Crystal structure of...) |
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| - | [[Image:2hka.gif|left|200px]]<br /><applet load="2hka" size=" | + | [[Image:2hka.gif|left|200px]]<br /><applet load="2hka" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2hka, resolution 1.81Å" /> | caption="2hka, resolution 1.81Å" /> | ||
'''Crystal structure of bovine NPC2 and cholesterol sulfate complex'''<br /> | '''Crystal structure of bovine NPC2 and cholesterol sulfate complex'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2HKA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with NAG, ACT, SO4, C3S and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2HKA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=ACT:'>ACT</scene>, <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=C3S:'>C3S</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HKA OCA]. |
==Reference== | ==Reference== | ||
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[[Category: beta barrel]] | [[Category: beta barrel]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 13:49:00 2008'' |
Revision as of 11:49, 23 January 2008
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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 with , , , and as ligands. 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 Wed Jan 23 13:49:00 2008
Categories: Bos taurus | Single protein | Benoff, B. | Gu, L. | Stock, A.M. | Xu, S. | ACT | C3S | GOL | NAG | SO4 | Beta barrel
