This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.


Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


2hka

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:2hka.gif|left|200px]]
+
{{Seed}}
 +
[[Image:2hka.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_2hka| PDB=2hka | SCENE= }}
{{STRUCTURE_2hka| PDB=2hka | SCENE= }}
-
'''Crystal structure of bovine NPC2 and cholesterol sulfate complex'''
+
===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.
+
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.
 +
-->
 +
{{ABSTRACT_PUBMED_17573352}}
==About this Structure==
==About this Structure==
Line 27: Line 31:
[[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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools