2qtw: Difference between revisions
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caption="2qtw, resolution 1.90Å" /> | caption="2qtw, resolution 1.90Å" /> | ||
'''The Crystal Structure of PCSK9 at 1.9 Angstroms Resolution Reveals structural homology to Resistin within the C-terminal domain'''<br /> | '''The Crystal Structure of PCSK9 at 1.9 Angstroms Resolution Reveals structural homology to Resistin within the C-terminal domain'''<br /> | ||
==Overview== | |||
Mutations in proprotein convertase subtilisin/kexin type 9 (PCSK9) are strongly associated with levels of low-density lipoprotein cholesterol in the blood plasma and, thereby, occurrence or resistance to atherosclerosis and coronary heart disease. Despite this importance, relatively little is known about the biology of PCSK9. Here, the crystal structure of a full-length construct of PCSK9 solved to 1.9-A resolution is presented. The structure contains a fully folded C-terminal cysteine-rich domain (CRD), showing a distinct structural similarity to the resistin homotrimer, a small cytokine associated with obesity and diabetes. This structural relationship between the CRD of PCSK9 and the resistin family is not observed in primary sequence comparisons and strongly suggests a distant evolutionary link between the two molecules. This three-dimensional homology provides insight into the function of PCSK9 at the molecular level and will help to dissect the link between PCSK9 and CHD. | |||
==Disease== | |||
Known diseases associated with this structure: Hypercholesterolemia, familial, 3 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607786 607786]] | |||
==About this Structure== | ==About this Structure== | ||
2QTW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene> and <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QTW OCA]. | 2QTW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene> and <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Sites: <scene name='pdbsite=AC1:Nag+Binding+Site+For+Residue+B+1001'>AC1</scene> and <scene name='pdbsite=AC2:Ca+Binding+Site+For+Residue+B+1'>AC2</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QTW OCA]. | ||
==Reference== | |||
The self-inhibited structure of full-length PCSK9 at 1.9 A reveals structural homology with resistin within the C-terminal domain., Hampton EN, Knuth MW, Li J, Harris JL, Lesley SA, Spraggon G, Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14604-9. Epub 2007 Sep 5. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17804797 17804797] | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Hampton, E | [[Category: Hampton, E N.]] | ||
[[Category: Harris, J | [[Category: Harris, J L.]] | ||
[[Category: Knuth, M | [[Category: Knuth, M W.]] | ||
[[Category: Lesley, S | [[Category: Lesley, S A.]] | ||
[[Category: Li, J.]] | [[Category: Li, J.]] | ||
[[Category: Spraggon, G.]] | [[Category: Spraggon, G.]] | ||
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[[Category: zymogen]] | [[Category: zymogen]] | ||
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