PCSK9: Difference between revisions

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<StructureSection load='2w2m' size='350' side='right' caption='Structure of human PCSK9 catalytic domain (grey) and prodomain (green) complex with LDL receptor EGF-A domain (magenta) and Ca+2 ion (PDB entry [[2w2m]])' scene=''>
<StructureSection load='' size='400' side='right' caption='Structure of human PCSK9 catalytic domain (blue) and prodomain (green) complex with LDL receptor EGF-A domain (magenta) and Ca+2 ion (PDB entry [[2w2m]])' scene='55/553967/Cv/2' pspeed='8'>
   
== Function ==   
'''PCSK9''' or '''Proprotein Convertase Subtilisin/Kexin type 9''' is a proteinase which is an enzyme which is part of cholesterol synthesis.  PCSK9 undergoes autocatalysis producing an active enzyme from its precursor.  PCSK9 binds to EGF-A domain of the LDL receptor (LDLR) inducing its degradation.  Low levels of LDL receptor are a cause of hypercholesterolemia since LDLR removes LDL cholesterol from the blood.  Thus PCSK9 is an important drug target as its level affects the amount of cholesterol in blood.
'''PCSK9''' or '''Proprotein Convertase Subtilisin/Kexin type 9''' is a proteinase which is part of the cholesterol synthesis<ref>PMID:17502100</ref>.  PCSK9 undergoes autocatalysis producing an active enzyme from its precursor.  PCSK9 binds to EGF-A domain of the LDL receptor (LDLR) inducing its degradation.  See details in [[Pro-protein convertase subtilisin/kexin type 9 (PCSK9)]].


== Relevance ==
Low levels of LDL receptor are a cause of hypercholesterolemia since LDLR removes LDL cholesterol from the blood.  Thus PCSK9 is an important drug target as its level affects the amount of cholesterol in blood<ref>PMID:23317404</ref>. Inhibition of PCSK9 results in increased pathogen lipid clearance, decreased inflammatory response and improved septic shock outcome<ref>PMID:25320235</ref>.
== Structural highlights ==
*<scene name='55/553967/Cv/7'>PCSK9 catalytic domain interactions with LDL receptor EGF-A domain</scene>. Water molecules are shown as red spheres.
*<scene name='55/553967/Cv/8'>PCSK9 Ca coordination site</scene>.
*<scene name='55/553967/Cv/9'>LDL receptor Ca coordination site</scene>.
</StructureSection>
==3D structures of PCSK9==
==3D structures of PCSK9==


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}


[[2p4e]], [[2pmw]], [[2qtw]] – hPCSK9 – human <br />
[[2p4e]], [[2pmw]], [[2qtw]], [[8wfr]] – hPCSK9 – human <br />
[[3bps]], [[2w2m]], [[3gcx]] – hPCSK9 + LDLR EGF-A <br />
[[3bps]], [[2w2m]], [[3gcx]] – hPCSK9 + LDLR EGF-A <br />
[[2w2n]], [[3gcw]] – hPCSK9 + LDLR EGF-A (mutant)<br />
[[2w2n]], [[3gcw]] – hPCSK9 + LDLR EGF-A (mutant)<br />
[[2w2o]], [[2w2p]], [[2w2q]] – hPCSK9 (mutant) + LDLR EGF-A <br />
[[2w2o]], [[2w2p]], [[2w2q]], [[7kev]], [[7kfa]] – hPCSK9 (mutant) + LDLR EGF-A <br />
[[2xtj]], [[3sqo]], [[4k8r]], [[5vl7]] – hPCSK9 + antibody <br />
[[3h42]] – hPCSK9 (mutant) + antibody <br />
[[3h42]] – hPCSK9 (mutant) + antibody <br />
[[2xtj]], [[3sqo]], [[4k8r]] – hPCSK9 + antibody <br />
[[6u26]], [[6u2n]], [[6u2p]] – hPCSK9 + inhibitor<br />
[[6u2f]], [[6u36]], [[6u38]], [[6u3i]], [[6u3x]] – hPCSK9 + antibody + inhibitor<br />
[[4nmx]], [[5vla]], [[5vlh]], [[5vkl]], [[5vll]], [[6xib]], [[6xic]], [[6xid]], [[6xie]], [[6xif]], [[7s5h]], [[8fpk]], [[8fpq]], [[8fvl]], [[8fvm]], [[8fvn]], [[8fvo]], [[8fvp]], [[8fvq]], [[8vdv]]  – hPCSK9 + peptide inhibitor<br />
[[6e4y]], [[6e4z]], [[6mv5]] – hPCSK9 N terminal + antibody <br />
[[7s5g]] – hPCSK9 + peptide + inhibitor<br />
[[6u2f]], [[6u3i]] – hPCSK9 + antibody + peptide inhibitor<br />
[[3m0c]] – hPCSK9 (mutant) + LDLR <br />
[[3m0c]] – hPCSK9 (mutant) + LDLR <br />
[[3p5b]], [[3p5c]] – hPCSK9 + LDLR variant <br />
[[3p5b]], [[3p5c]] – hPCSK9 + LDLR variant <br />
[[4ov6]] – hPCSK9 + adnectin <br />
[[7anq]] – hPCSK9 C terminal + VHH minibody <br />
[[6olz]], [[6om0]], [[6om7]] – hPCSK9 in ribosome – Cryo EM <br />
== References ==
<references/>
[[Category:Topic Page]]

Latest revision as of 08:50, 20 April 2026

Structure of human PCSK9 catalytic domain (blue) and prodomain (green) complex with LDL receptor EGF-A domain (magenta) and Ca+2 ion (PDB entry 2w2m)

Drag the structure with the mouse to rotate

3D structures of PCSK9

Updated on 20-April-2026

Pro-protein convertase subtilisin/kexin type 9 (PCSK9), 2pmw, 2qtw, 8wfr – hPCSK9 – human
3bps, 2w2m, 3gcx – hPCSK9 + LDLR EGF-A
2w2n, 3gcw – hPCSK9 + LDLR EGF-A (mutant)
2w2o, 2w2p, 2w2q, 7kev, 7kfa – hPCSK9 (mutant) + LDLR EGF-A
2xtj, 3sqo, 4k8r, 5vl7 – hPCSK9 + antibody
3h42 – hPCSK9 (mutant) + antibody
6u26, 6u2n, 6u2p – hPCSK9 + inhibitor
6u2f, 6u36, 6u38, 6u3i, 6u3x – hPCSK9 + antibody + inhibitor
4nmx, 5vla, 5vlh, 5vkl, 5vll, 6xib, 6xic, 6xid, 6xie, 6xif, 7s5h, 8fpk, 8fpq, 8fvl, 8fvm, 8fvn, 8fvo, 8fvp, 8fvq, 8vdv – hPCSK9 + peptide inhibitor
6e4y, 6e4z, 6mv5 – hPCSK9 N terminal + antibody
7s5g – hPCSK9 + peptide + inhibitor
6u2f, 6u3i – hPCSK9 + antibody + peptide inhibitor
3m0c – hPCSK9 (mutant) + LDLR
3p5b, 3p5c – hPCSK9 + LDLR variant
4ov6 – hPCSK9 + adnectin
7anq – hPCSK9 C terminal + VHH minibody
6olz, 6om0, 6om7 – hPCSK9 in ribosome – Cryo EM

References

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman