3bps

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[[Image:3bps.jpg|left|200px]]<br /><applet load="3bps" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:3bps.jpg|left|200px]]
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caption="3bps, resolution 2.41&Aring;" />
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'''PCSK9:EGF-A complex'''<br />
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{{Structure
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|PDB= 3bps |SIZE=350|CAPTION= <scene name='initialview01'>3bps</scene>, resolution 2.41&Aring;
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|SITE= <scene name='pdbsite=AC1:Ca+Binding+Site+For+Residue+E+1'>AC1</scene>
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|LIGAND= <scene name='pdbligand=CA:CALCIUM ION'>CA</scene>
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|ACTIVITY=
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|GENE= PCSK9, NARC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), LDLR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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}}
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'''PCSK9:EGF-A complex'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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3BPS 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=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Site: <scene name='pdbsite=AC1:Ca+Binding+Site+For+Residue+E+1'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BPS OCA].
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3BPS is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BPS OCA].
==Reference==
==Reference==
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Molecular basis for LDL receptor recognition by PCSK9., Kwon HJ, Lagace TA, McNutt MC, Horton JD, Deisenhofer J, Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):1820-5. Epub 2008 Feb 4. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18250299 18250299]
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Molecular basis for LDL receptor recognition by PCSK9., Kwon HJ, Lagace TA, McNutt MC, Horton JD, Deisenhofer J, Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):1820-5. Epub 2008 Feb 4. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18250299 18250299]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Protein complex]]
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[[Category: zymogen]]
[[Category: zymogen]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 27 07:48:45 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 19:00:35 2008''

Revision as of 17:00, 20 March 2008

Image:3bps.jpg


PDB ID 3bps

Drag the structure with the mouse to rotate
, resolution 2.41Å
Sites:
Ligands:
Gene: PCSK9, NARC1 (Homo sapiens), LDLR (Homo sapiens)
Coordinates: save as pdb, mmCIF, xml



PCSK9:EGF-A complex


Overview

Proprotein convertase subtilisin/kexin type 9 (PCSK9) posttranslationally regulates hepatic low-density lipoprotein receptors (LDLRs) by binding to LDLRs on the cell surface, leading to their degradation. The binding site of PCSK9 has been localized to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR. Here, we describe the crystal structure of a complex between PCSK9 and the EGF-A domain of the LDLR. The binding site for the LDLR EGF-A domain resides on the surface of PCSK9's subtilisin-like catalytic domain containing Asp-374, a residue for which a gain-of-function mutation (Asp-374-Tyr) increases the affinity of PCSK9 toward LDLR and increases plasma LDL-cholesterol (LDL-C) levels in humans. The binding surface on PCSK9 is distant from its catalytic site, and the EGF-A domain makes no contact with either the C-terminal domain or the prodomain. Point mutations in PCSK9 that altered key residues contributing to EGF-A binding (Arg-194 and Phe-379) greatly diminished binding to the LDLR's extracellular domain. The structure of PCSK9 in complex with the LDLR EGF-A domain defines potential therapeutic target sites for blocking agents that could interfere with this interaction in vivo, thereby increasing LDLR function and reducing plasma LDL-C levels.

About this Structure

3BPS is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Molecular basis for LDL receptor recognition by PCSK9., Kwon HJ, Lagace TA, McNutt MC, Horton JD, Deisenhofer J, Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):1820-5. Epub 2008 Feb 4. PMID:18250299

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