PCSK9: Difference between revisions
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<StructureSection load=' | <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 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. | '''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 /> | ||
[[ | [[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]] | [[Category:Topic Page]] | ||
