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- PDB-2p4e: Crystal Structure of PCSK9 -

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Basic information

Entry
Database: PDB / ID: 2p4e
TitleCrystal Structure of PCSK9
ComponentsProprotein convertase subtilisin/kexin type 9
KeywordsHYDROLASE / protease / subtilisin / LDL receptor / LDL / endocytosis
Function / homology
Function and homology information


negative regulation of low-density lipoprotein particle receptor binding / negative regulation of receptor-mediated endocytosis involved in cholesterol transport / low-density lipoprotein particle receptor catabolic process / extrinsic component of external side of plasma membrane / PCSK9-LDLR complex / very-low-density lipoprotein particle binding / negative regulation of receptor recycling / PCSK9-AnxA2 complex / negative regulation of sodium ion transmembrane transporter activity / apolipoprotein receptor binding ...negative regulation of low-density lipoprotein particle receptor binding / negative regulation of receptor-mediated endocytosis involved in cholesterol transport / low-density lipoprotein particle receptor catabolic process / extrinsic component of external side of plasma membrane / PCSK9-LDLR complex / very-low-density lipoprotein particle binding / negative regulation of receptor recycling / PCSK9-AnxA2 complex / negative regulation of sodium ion transmembrane transporter activity / apolipoprotein receptor binding / negative regulation of low-density lipoprotein particle clearance / low-density lipoprotein particle binding / signaling receptor inhibitor activity / LDL clearance / positive regulation of low-density lipoprotein particle receptor catabolic process / lipoprotein metabolic process / very-low-density lipoprotein particle receptor binding / negative regulation of low-density lipoprotein receptor activity / negative regulation of receptor internalization / endolysosome membrane / regulation of signaling receptor activity / sodium channel inhibitor activity / lysosomal transport / low-density lipoprotein particle receptor binding / triglyceride metabolic process / COPII-coated ER to Golgi transport vesicle / apolipoprotein binding / positive regulation of receptor internalization / protein autoprocessing / Hydrolases; Acting on peptide bonds (peptidases); Serine endopeptidases / phospholipid metabolic process / regulation of neuron apoptotic process / VLDLR internalisation and degradation / cellular response to starvation / cholesterol metabolic process / neurogenesis / liver development / kidney development / cholesterol homeostasis / Post-translational protein phosphorylation / neuron differentiation / cellular response to insulin stimulus / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / : / positive regulation of neuron apoptotic process / late endosome / lysosome / early endosome / endoplasmic reticulum lumen / lysosomal membrane / serine-type endopeptidase activity / apoptotic process / perinuclear region of cytoplasm / Golgi apparatus / cell surface / endoplasmic reticulum / RNA binding / extracellular space / extracellular region / plasma membrane / cytoplasm
Similarity search - Function
Proprotein convertase subtilisin/kexin type 9 / Proprotein convertase subtilisin/kexin type 9, C-terminal domain 3 / Proprotein convertase subtilisin/kexin type 9, C-terminal domain 2 / Proprotein convertase subtilisin/kexin type 9, C-terminal domain 1 / Proprotein convertase subtilisin-like/kexin type 9 C-terminal domain / Proprotein convertase subtilisin-like/kexin type 9 C-terminal domain / Proprotein convertase subtilisin-like/kexin type 9 C-terminal domain / Peptidase S8 propeptide/proteinase inhibitor I9 / Proteinase K-like catalytic domain / Peptidase S8/S53 domain ...Proprotein convertase subtilisin/kexin type 9 / Proprotein convertase subtilisin/kexin type 9, C-terminal domain 3 / Proprotein convertase subtilisin/kexin type 9, C-terminal domain 2 / Proprotein convertase subtilisin/kexin type 9, C-terminal domain 1 / Proprotein convertase subtilisin-like/kexin type 9 C-terminal domain / Proprotein convertase subtilisin-like/kexin type 9 C-terminal domain / Proprotein convertase subtilisin-like/kexin type 9 C-terminal domain / Peptidase S8 propeptide/proteinase inhibitor I9 / Proteinase K-like catalytic domain / Peptidase S8/S53 domain / Peptidase S8 propeptide/proteinase inhibitor I9 / Peptidase inhibitor I9 / Peptidase S8 propeptide/proteinase inhibitor I9 superfamily / Serine proteases, subtilase domain profile. / Peptidase S8, subtilisin-related / Peptidase S8/S53 domain superfamily / Subtilase family / Peptidase S8/S53 domain / Jelly Rolls / Alpha-Beta Plaits / Sandwich / Rossmann fold / 2-Layer Sandwich / 3-Layer(aba) Sandwich / Mainly Beta / Alpha Beta
Similarity search - Domain/homology
: / Proprotein convertase subtilisin/kexin type 9
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.98 Å
AuthorsCunningham, D. / Danley, D.E. / Geoghegan, F.K. / Griffor, M.C. / Hawkins, J.L. / Qiu, X.
CitationJournal: Nat.Struct.Mol.Biol. / Year: 2007
Title: Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia.
Authors: Cunningham, D. / Danley, D.E. / Geoghegan, K.F. / Griffor, M.C. / Hawkins, J.L. / Subashi, T.A. / Varghese, A.H. / Ammirati, M.J. / Culp, J.S. / Hoth, L.R. / Mansour, M.N. / McGrath, K.M. / ...Authors: Cunningham, D. / Danley, D.E. / Geoghegan, K.F. / Griffor, M.C. / Hawkins, J.L. / Subashi, T.A. / Varghese, A.H. / Ammirati, M.J. / Culp, J.S. / Hoth, L.R. / Mansour, M.N. / McGrath, K.M. / Seddon, A.P. / Shenolikar, S. / Stutzman-Engwall, K.J. / Warren, L.C. / Xia, D. / Qiu, X.
History
DepositionMar 12, 2007Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 10, 2007Provider: repository / Type: Initial release
Revision 1.1May 1, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Derived calculations / Version format compliance
Revision 1.3Aug 30, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / pdbx_struct_conn_angle / struct_conn / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_conn_angle.ptnr1_auth_asym_id / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
P: Proprotein convertase subtilisin/kexin type 9
A: Proprotein convertase subtilisin/kexin type 9
hetero molecules


Theoretical massNumber of molelcules
Total (without water)149,3244
Polymers148,9232
Non-polymers4012
Water6,684371
1
P: Proprotein convertase subtilisin/kexin type 9
hetero molecules


Theoretical massNumber of molelcules
Total (without water)74,8623
Polymers74,4611
Non-polymers4012
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
A: Proprotein convertase subtilisin/kexin type 9


Theoretical massNumber of molelcules
Total (without water)74,4611
Polymers74,4611
Non-polymers00
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3


  • Idetical with deposited unit
  • defined by software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2950 Å2
ΔGint-71 kcal/mol
Surface area24860 Å2
MethodPISA, PQS
Unit cell
Length a, b, c (Å)62.810, 70.670, 150.020
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

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Components

#1: Protein Proprotein convertase subtilisin/kexin type 9 / Proprotein convertase PC9 / Subtilisin/kexin-like protease PC9 / Neural apoptosis-regulated ...Proprotein convertase PC9 / Subtilisin/kexin-like protease PC9 / Neural apoptosis-regulated convertase 1 / NARC-1


Mass: 74461.289 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PCSK9, NARC1 / Plasmid: PCSK9 / Production host: Cricetulus griseus (Chinese hamster)
References: UniProt: Q8NBP7, Hydrolases; Acting on peptide bonds (peptidases); Serine endopeptidases
#2: Chemical ChemComp-HG / MERCURY (II) ION


Mass: 200.590 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Hg
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 371 / Source method: isolated from a natural source / Formula: H2O

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

Crystal growTemperature: 300 K / Method: vapor diffusion, hanging drop / pH: 8.5
Details: 25% PEG 1500, 50 mM Tris-HCl buffer, pH 8.5, VAPOR DIFFUSION, HANGING DROP, temperature 300K

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 210 / Detector: CCD / Date: Apr 1, 2006 / Details: mirros
RadiationMonochromator: mirror / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.98→75 Å / Num. all: 48000 / Num. obs: 46285 / % possible obs: 97.9 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 2 / Redundancy: 6.6 % / Rmerge(I) obs: 0.115 / Net I/σ(I): 15.4
Reflection shellResolution: 1.98→2.05 Å / Redundancy: 4.3 % / Rmerge(I) obs: 0.57 / Mean I/σ(I) obs: 2 / % possible all: 84.4

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Processing

Software
NameVersionClassification
CrystalClear(MSC/RIGAKU)data collection
AMoREphasing
REFMAC5.1refinement
HKL-2000data reduction
HKL-2000data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1IC6

1ic6


Resolution: 1.98→75 Å / Isotropic thermal model: individual isotropic / Cross valid method: THROUGHOUT / σ(F): 0 / σ(I): 0 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflectionSelection details
Rfree0.25 2339 -RANDOM
Rwork0.2 ---
all0.202 43933 --
obs0.202 43933 97.9 %-
Refine analyzeLuzzati coordinate error obs: 0.18 Å
Refinement stepCycle: LAST / Resolution: 1.98→75 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4398 0 2 371 4771
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONc_angle_d0.011
X-RAY DIFFRACTIONc_angle_deg1.3

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