PCSK9
From Proteopedia
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| - | <StructureSection load='' size='400' side='right' caption='Structure of human PCSK9 catalytic domain ( | + | <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 == | == Function == | ||
| - | '''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. | + | '''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 == | == Relevance == | ||
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== Structural highlights == | == Structural highlights == | ||
| - | *<scene name='55/553967/Cv/ | + | *<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/ | + | *<scene name='55/553967/Cv/8'>PCSK9 Ca coordination site</scene>. |
| - | *<scene name='55/553967/Cv/ | + | *<scene name='55/553967/Cv/9'>LDL receptor Ca coordination site</scene>. |
</StructureSection> | </StructureSection> | ||
==3D structures of PCSK9== | ==3D structures of PCSK9== | ||
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[[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 | + | [[2w2o]], [[2w2p]], [[2w2q]], [[7kev]], [[7kfa]] – hPCSK9 (mutant) + LDLR EGF-A <br /> |
| - | + | ||
[[2xtj]], [[3sqo]], [[4k8r]] – hPCSK9 + antibody <br /> | [[2xtj]], [[3sqo]], [[4k8r]] – hPCSK9 + antibody <br /> | ||
| + | [[3h42]] – hPCSK9 (mutant) + antibody <br /> | ||
| + | [[6e4y]], [[6e4z]], [[6mv5]] – hPCSK9 N terminal + antibody <br /> | ||
| + | [[6u26]], [[6u2n]], [[6u2p]] – hPCSK9 + inhibitor<br /> | ||
| + | [[6u2f]], [[6u36]], [[6u38]], [[6u3i]], [[6u3x]] – hPCSK9 + antibody + inhibitor<br /> | ||
| + | [[6xib]], [[6xic]], [[6xid]], [[6xie]], [[6xif]], [[7s5h]] – hPCSK9 + peptide <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 /> | [[4ov6]] – hPCSK9 + adnectin <br /> | ||
| + | [[7anq]] – hPCSK9 C terminal + VHH minibody <br /> | ||
| + | [[6olz]], [[6om0]], [[6om7]] – hPCSK9 in ribosome – Cryo EM <br /> | ||
| + | |||
== References == | == References == | ||
<references/> | <references/> | ||
[[Category:Topic Page]] | [[Category:Topic Page]] | ||
Current revision
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3D structures of PCSK9
Updated on 05-December-2021
2p4e, 2pmw, 2qtw – 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 – hPCSK9 + antibody
3h42 – hPCSK9 (mutant) + antibody
6e4y, 6e4z, 6mv5 – hPCSK9 N terminal + antibody
6u26, 6u2n, 6u2p – hPCSK9 + inhibitor
6u2f, 6u36, 6u38, 6u3i, 6u3x – hPCSK9 + antibody + inhibitor
6xib, 6xic, 6xid, 6xie, 6xif, 7s5h – hPCSK9 + peptide
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
- ↑ Piper DE, Jackson S, Liu Q, Romanow WG, Shetterly S, Thibault ST, Shan B, Walker NP. The crystal structure of PCSK9: a regulator of plasma LDL-cholesterol. Structure. 2007 May;15(5):545-52. PMID:17502100 doi:http://dx.doi.org/10.1016/j.str.2007.04.004
- ↑ Seidah NG. Proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors in the treatment of hypercholesterolemia and other pathologies. Curr Pharm Des. 2013;19(17):3161-72. PMID:23317404
- ↑ Walley KR, Thain KR, Russell JA, Reilly MP, Meyer NJ, Ferguson JF, Christie JD, Nakada TA, Fjell CD, Thair SA, Cirstea MS, Boyd JH. PCSK9 is a critical regulator of the innate immune response and septic shock outcome. Sci Transl Med. 2014 Oct 15;6(258):258ra143. doi: 10.1126/scitranslmed.3008782. PMID:25320235 doi:http://dx.doi.org/10.1126/scitranslmed.3008782
