2obd: Difference between revisions

[[Image:2obd.gif|left|200px]]<br /><applet load="2obd" size="350" color="white" frame="true" align="right" spinBox="true"  

Cholesteryl ester transfer protein (CETP) shuttles various lipids between lipoproteins, resulting in the net transfer of cholesteryl esters from atheroprotective, high-density lipoproteins (HDL) to atherogenic, lower-density species. Inhibition of CETP raises HDL cholesterol and may potentially be used to treat cardiovascular disease. Here we describe the structure of CETP at 2.2-A resolution, revealing a 60-A-long tunnel filled with two hydrophobic cholesteryl esters and plugged by an amphiphilic phosphatidylcholine at each end. The two tunnel openings are large enough to allow lipid access, which is aided by a flexible helix and possibly also by a mobile flap. The curvature of the concave surface of CETP matches the radius of curvature of HDL particles, and potential conformational changes may occur to accommodate larger lipoprotein particles. Point mutations blocking the middle of the tunnel abolish lipid-transfer activities, suggesting that neutral lipids pass through this continuous tunnel.

Known diseases associated with this structure: CETP deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=118470 118470]], High density lipoprotein cholesterol level QTL 10 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=118470 118470]], Hyperalphalipoproteinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=118470 118470]], Longevity, exceptional OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=118470 118470]]

2OBD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=2OB:'>2OB</scene>, <scene name='pdbligand=PCW:'>PCW</scene>, <scene name='pdbligand=EPE:'>EPE</scene>, <scene name='pdbligand=1PE:'>1PE</scene> and <scene name='pdbligand=PG4:'>PG4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OBD OCA].  

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