[English] 日本語
Yorodumi
- PDB-8b4x: X-ray structure of furin (PCSK3) in complex with Guanidinomethyl-... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8b4x
TitleX-ray structure of furin (PCSK3) in complex with Guanidinomethyl-Phac-R-Tle-K-6-(aminomethyl)-3-amino-isoindol
Components
  • Furin
  • Guanidinomethyl-Phac-R-Tle-K-6-(aminomethyl)-3-amino-isoindol
KeywordsHYDROLASE / furin / proprotein convertase subtilisin/kexin type 3 / PCSK3 / SARS-CoV-2 / inhibitor / protease / complex
Function / homology
Function and homology information


furin / nerve growth factor production / dibasic protein processing / plasma lipoprotein particle remodeling / NGF processing / negative regulation of transforming growth factor beta1 production / Assembly of active LPL and LIPC lipase complexes / regulation of cholesterol transport / signal peptide processing / negative regulation of low-density lipoprotein particle receptor catabolic process ...furin / nerve growth factor production / dibasic protein processing / plasma lipoprotein particle remodeling / NGF processing / negative regulation of transforming growth factor beta1 production / Assembly of active LPL and LIPC lipase complexes / regulation of cholesterol transport / signal peptide processing / negative regulation of low-density lipoprotein particle receptor catabolic process / peptide biosynthetic process / Pre-NOTCH Processing in Golgi / nerve growth factor binding / Synthesis and processing of ENV and VPU / cytokine precursor processing / Formation of the cornified envelope / secretion by cell / Signaling by PDGF / trans-Golgi network transport vesicle / Signaling by NODAL / heparan sulfate binding / blastocyst formation / Elastic fibre formation / peptide hormone processing / positive regulation of membrane protein ectodomain proteolysis / zymogen activation / CD163 mediating an anti-inflammatory response / Activation of Matrix Metalloproteinases / Maturation of hRSV A proteins / regulation of protein catabolic process / TGF-beta receptor signaling activates SMADs / Collagen degradation / collagen catabolic process / Respiratory syncytial virus (RSV) attachment and entry / Uptake and function of anthrax toxins / extracellular matrix disassembly / regulation of signal transduction / endopeptidase activator activity / Removal of aminoterminal propeptides from gamma-carboxylated proteins / viral life cycle / extracellular matrix organization / serine-type peptidase activity / peptide binding / transforming growth factor beta receptor signaling pathway / protein maturation / negative regulation of inflammatory response to antigenic stimulus / serine-type endopeptidase inhibitor activity / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / trans-Golgi network / protein processing / Golgi lumen / peptidase activity / heparin binding / protease binding / endopeptidase activity / viral translation / amyloid fibril formation / Potential therapeutics for SARS / Induction of Cell-Cell Fusion / Attachment and Entry / positive regulation of viral entry into host cell / endosome membrane / viral protein processing / membrane raft / Amyloid fiber formation / Golgi membrane / serine-type endopeptidase activity / cell surface / endoplasmic reticulum / extracellular exosome / extracellular region / metal ion binding / membrane / plasma membrane
Similarity search - Function
Peptidase S8, pro-domain / Peptidase S8, pro-domain superfamily / Peptidase S8 pro-domain / Kexin/furin catalytic domain / P domain / Proprotein convertase P-domain / P/Homo B domain profile. / Peptidase S8, subtilisin, His-active site / Serine proteases, subtilase family, histidine active site. / Serine proteases, subtilase family, aspartic acid active site. ...Peptidase S8, pro-domain / Peptidase S8, pro-domain superfamily / Peptidase S8 pro-domain / Kexin/furin catalytic domain / P domain / Proprotein convertase P-domain / P/Homo B domain profile. / Peptidase S8, subtilisin, His-active site / Serine proteases, subtilase family, histidine active site. / Serine proteases, subtilase family, aspartic acid active site. / Peptidase S8, subtilisin, Asp-active site / Serine proteases, subtilase family, serine active site. / Peptidase S8, subtilisin, Ser-active site / Peptidase S8, subtilisin-related / Serine proteases, subtilase domain profile. / Peptidase S8/S53 domain superfamily / Subtilase family / Peptidase S8/S53 domain / Furin-like repeat / Furin-like repeats / Growth factor receptor cysteine-rich domain superfamily / Galactose-binding-like domain superfamily
Similarity search - Domain/homology
Biological speciesHomo sapiens (human)
synthetic construct (others)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.6 Å
AuthorsDahms, S.O. / Brandstetter, H.
Funding support Austria, 1items
OrganizationGrant numberCountry
Austrian Science FundM 2730 Austria
CitationJournal: Chemmedchem / Year: 2024
Title: Fragment-Based Design, Synthesis, and Characterization of Aminoisoindole-Derived Furin Inhibitors.
Authors: Lange, R.W. / Bloch, K. / Heindl, M.R. / Wollenhaupt, J. / Weiss, M.S. / Brandstetter, H. / Klebe, G. / Falcone, F.H. / Bottcher-Friebertshauser, E. / Dahms, S.O. / Steinmetzer, T.
History
DepositionSep 21, 2022Deposition site: PDBE / Processing site: PDBE
Revision 1.0Oct 4, 2023Provider: repository / Type: Initial release
Revision 1.1Mar 13, 2024Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2May 15, 2024Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation_author.identifier_ORCID

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Furin
B: Guanidinomethyl-Phac-R-Tle-K-6-(aminomethyl)-3-amino-isoindol
hetero molecules


Theoretical massNumber of molelcules
Total (without water)53,26712
Polymers52,8632
Non-polymers40410
Water8,197455
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2300 Å2
ΔGint-58 kcal/mol
Surface area17630 Å2
MethodPISA
Unit cell
Length a, b, c (Å)132.049, 132.049, 155.492
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number179
Space group name H-MP6522
Space group name HallP652(x,y,z+1/12)
Symmetry operation#1: x,y,z
#2: x-y,x,z+5/6
#3: y,-x+y,z+1/6
#4: -y,x-y,z+2/3
#5: -x+y,-x,z+1/3
#6: x-y,-y,-z
#7: -x,-x+y,-z+1/3
#8: -x,-y,z+1/2
#9: y,x,-z+2/3
#10: -y,-x,-z+1/6
#11: -x+y,y,-z+1/2
#12: x,x-y,-z+5/6
Components on special symmetry positions
IDModelComponents
11A-606-

NA

21A-607-

NA

31A-1081-

HOH

-
Components

-
Protein / Protein/peptide , 2 types, 2 molecules AB

#1: Protein Furin / Dibasic-processing enzyme / Paired basic amino acid residue-cleaving enzyme / PACE


Mass: 52112.312 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: FURIN, FUR, PACE, PCSK3 / Cell line (production host): HEK293S / Production host: Homo sapiens (human) / References: UniProt: P09958, furin
#2: Protein/peptide Guanidinomethyl-Phac-R-Tle-K-6-(aminomethyl)-3-amino-isoindol


Mass: 750.957 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others)

-
Non-polymers , 5 types, 465 molecules

#3: Chemical ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: Ca
#4: Chemical
ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Na
#5: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Cl
#6: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 455 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.75 Å3/Da / Density % sol: 67.24 %
Crystal growTemperature: 293.15 K / Method: vapor diffusion, sitting drop
Details: CRYSTALLIZATION SOLUTION: 100mM MES, 200mM K/NAH2PO4, PH 5.5, 2 M NACL; RESERVOIR SOLUTION: 3.0-3.2M NACL

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID30B / Wavelength: 0.968626 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Sep 27, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.968626 Å / Relative weight: 1
ReflectionResolution: 1.6→46.06 Å / Num. obs: 104100 / % possible obs: 99 % / Redundancy: 19 % / Biso Wilson estimate: 23.44 Å2 / CC1/2: 0.999 / Rrim(I) all: 0.153 / Net I/σ(I): 13.81
Reflection shellResolution: 1.6→1.7 Å / Mean I/σ(I) obs: 1.22 / Num. unique obs: 16441 / CC1/2: 0.513 / Rrim(I) all: 3.276 / % possible all: 98.1

-
Processing

Software
NameVersionClassification
PHENIX1.20.1_4487refinement
PHENIX1.20.1_4487phasing
XDSVERSION Jan 31, 2020data reduction
XDSVERSION Jan 31, 2020data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5jxh

5jxh


Resolution: 1.6→46.06 Å / SU ML: 0.1922 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 17.7426
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.1695 5165 4.96 %
Rwork0.158 98887 -
obs0.1585 104052 98.98 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 28.95 Å2
Refinement stepCycle: LAST / Resolution: 1.6→46.06 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3608 0 70 455 4133
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00753904
X-RAY DIFFRACTIONf_angle_d0.9685338
X-RAY DIFFRACTIONf_chiral_restr0.0548576
X-RAY DIFFRACTIONf_plane_restr0.0092713
X-RAY DIFFRACTIONf_dihedral_angle_d12.26511445
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.6-1.620.34341630.32853231X-RAY DIFFRACTION98.04
1.62-1.640.35161630.3173209X-RAY DIFFRACTION97.85
1.64-1.660.31221730.30493236X-RAY DIFFRACTION98.13
1.66-1.680.30221710.28543187X-RAY DIFFRACTION98.24
1.68-1.70.27921870.27183222X-RAY DIFFRACTION98.3
1.7-1.720.2461770.26113215X-RAY DIFFRACTION98.35
1.72-1.750.25722050.24523187X-RAY DIFFRACTION98.18
1.75-1.770.24781460.22663270X-RAY DIFFRACTION98.53
1.77-1.80.22961680.21023247X-RAY DIFFRACTION98.53
1.8-1.830.21681960.20273213X-RAY DIFFRACTION98.61
1.83-1.860.2181570.19313252X-RAY DIFFRACTION98.61
1.86-1.90.22941760.18383247X-RAY DIFFRACTION98.62
1.9-1.930.19331770.17653254X-RAY DIFFRACTION98.88
1.93-1.970.19511630.16343281X-RAY DIFFRACTION98.85
1.97-2.020.17671470.16063284X-RAY DIFFRACTION98.88
2.02-2.060.19321700.15313304X-RAY DIFFRACTION99.2
2.06-2.110.15571770.14183235X-RAY DIFFRACTION99.04
2.11-2.170.14951750.13123301X-RAY DIFFRACTION99.12
2.17-2.240.14381710.12823280X-RAY DIFFRACTION99.08
2.24-2.310.15231490.12673307X-RAY DIFFRACTION99.14
2.31-2.390.15791560.12813325X-RAY DIFFRACTION99.32
2.39-2.490.14121630.13663333X-RAY DIFFRACTION99.52
2.49-2.60.16071580.14163341X-RAY DIFFRACTION99.52
2.6-2.740.17251700.15593335X-RAY DIFFRACTION99.66
2.74-2.910.18531860.16073323X-RAY DIFFRACTION99.72
2.91-3.130.16361640.1573395X-RAY DIFFRACTION99.8
3.13-3.450.15711950.14473362X-RAY DIFFRACTION99.89
3.45-3.940.12711770.1263416X-RAY DIFFRACTION99.97
3.95-4.970.12251860.11873455X-RAY DIFFRACTION100
4.97-46.060.17871990.19043640X-RAY DIFFRACTION99.74
Refinement TLS params.Method: refined / Origin x: 35.3403029172 Å / Origin y: -37.8053366253 Å / Origin z: 0.128744691874 Å
111213212223313233
T0.170693660422 Å2-0.00831296121248 Å20.00742311605447 Å2-0.214050241005 Å2-0.00111421937122 Å2--0.208006922052 Å2
L0.420080119593 °20.0983947186962 °2-0.0711591920779 °2-0.55660905735 °20.260583656134 °2--0.758502189001 °2
S-0.0128032760368 Å °0.0461037434492 Å °-0.0272691968828 Å °-0.0593369118908 Å °0.00961796114022 Å °0.0228719477898 Å °-0.00804550316426 Å °-0.0764836236194 Å °-4.31170865434E-6 Å °
Refinement TLS groupSelection details: chain A

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more