[English] 日本語
Yorodumi
- PDB-6yd7: X-ray structure of furin in complex with the canavanine-based inh... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6yd7
TitleX-ray structure of furin in complex with the canavanine-based inhibitor 4-guanidinomethyl-phenylacetyl-Arg-Tle-Canavanine-Amba
Components
  • 4-guanidinomethyl-phenylacetyl-Arg-Tle-Canavanine-Amba
  • Furin
KeywordsHYDROLASE / Protease / Inhibitor / Complex / Canavanine
Function / homology
Function and homology information


furin / nerve growth factor production / dibasic protein processing / plasma lipoprotein particle remodeling / NGF processing / Assembly of active LPL and LIPC lipase complexes / negative regulation of transforming growth factor beta1 production / signal peptide processing / regulation of cholesterol transport / peptide biosynthetic process ...furin / nerve growth factor production / dibasic protein processing / plasma lipoprotein particle remodeling / NGF processing / Assembly of active LPL and LIPC lipase complexes / negative regulation of transforming growth factor beta1 production / signal peptide processing / regulation of cholesterol transport / peptide biosynthetic process / negative regulation of low-density lipoprotein particle receptor catabolic process / cytokine precursor processing / Pre-NOTCH Processing in Golgi / secretion by cell / Synthesis and processing of ENV and VPU / Formation of the cornified envelope / nerve growth factor binding / Signaling by PDGF / trans-Golgi network transport vesicle / Elastic fibre formation / blastocyst formation / Signaling by NODAL / heparan sulfate binding / regulation of endopeptidase activity / positive regulation of membrane protein ectodomain proteolysis / zymogen activation / peptide hormone processing / CD163 mediating an anti-inflammatory response / regulation of protein catabolic process / Activation of Matrix Metalloproteinases / Maturation of hRSV A proteins / TGF-beta receptor signaling activates SMADs / Respiratory syncytial virus (RSV) attachment and entry / Uptake and function of anthrax toxins / protein maturation / Collagen degradation / collagen catabolic process / extracellular matrix disassembly / regulation of signal transduction / Removal of aminoterminal propeptides from gamma-carboxylated proteins / negative regulation of inflammatory response to antigenic stimulus / viral life cycle / serine-type peptidase activity / extracellular matrix organization / transforming growth factor beta receptor signaling pathway / peptide binding / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / serine-type endopeptidase inhibitor activity / trans-Golgi network / protein processing / Golgi lumen / peptidase activity / heparin binding / viral translation / endopeptidase activity / protease binding / amyloid fibril formation / Induction of Cell-Cell Fusion / Potential therapeutics for SARS / Attachment and Entry / positive regulation of viral entry into host cell / viral protein processing / endosome membrane / membrane raft / Amyloid fiber formation / Golgi membrane / serine-type endopeptidase activity / cell surface / endoplasmic reticulum / extracellular exosome / extracellular region / membrane / metal ion binding / 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 / Serine proteases, subtilase domain profile. / Peptidase S8, subtilisin-related / Furin-like repeat / Furin-like repeats / Peptidase S8/S53 domain superfamily / Subtilase family / Peptidase S8/S53 domain / Growth factor receptor cysteine-rich domain superfamily / Galactose-binding-like domain superfamily
Similarity search - Domain/homology
PHOSPHATE ION / Furin
Similarity search - Component
Biological speciesHomo sapiens (human)
synthetic construct (others)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.8 Å
AuthorsDahms, S.O.
Funding support Austria, 1items
OrganizationGrant numberCountry
Austrian Science FundM 2730 Austria
CitationJournal: Acs Med.Chem.Lett. / Year: 2021
Title: The Basicity Makes the Difference: Improved Canavanine-Derived Inhibitors of the Proprotein Convertase Furin.
Authors: Lam van, T.V. / Heindl, M.R. / Schlutt, C. / Bottcher-Friebertshauser, E. / Bartenschlager, R. / Klebe, G. / Brandstetter, H. / Dahms, S.O. / Steinmetzer, T.
History
DepositionMar 20, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0Feb 17, 2021Provider: repository / Type: Initial release
Revision 1.1Mar 31, 2021Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.name
Revision 2.0Oct 19, 2022Group: Advisory / Atomic model ...Advisory / Atomic model / Data collection / Database references / Derived calculations / Non-polymer description / Polymer sequence / Source and taxonomy / Structure summary
Category: atom_site / chem_comp ...atom_site / chem_comp / database_2 / entity / entity_poly / entity_poly_seq / entity_src_gen / pdbx_entity_nonpoly / pdbx_entity_src_syn / pdbx_nonpoly_scheme / pdbx_poly_seq_scheme / pdbx_struct_assembly / pdbx_struct_assembly_gen / pdbx_struct_assembly_prop / pdbx_struct_conn_angle / pdbx_struct_sheet_hbond / pdbx_struct_special_symmetry / pdbx_unobs_or_zero_occ_atoms / struct_asym / struct_conn / struct_ref / struct_ref_seq / struct_sheet / struct_sheet_order / struct_sheet_range / struct_site / struct_site_gen
Item: _atom_site.B_iso_or_equiv / _atom_site.Cartn_x ..._atom_site.B_iso_or_equiv / _atom_site.Cartn_x / _atom_site.Cartn_y / _atom_site.Cartn_z / _atom_site.auth_asym_id / _atom_site.auth_atom_id / _atom_site.auth_comp_id / _atom_site.auth_seq_id / _atom_site.group_PDB / _atom_site.label_alt_id / _atom_site.label_asym_id / _atom_site.label_atom_id / _atom_site.label_comp_id / _atom_site.label_entity_id / _atom_site.label_seq_id / _atom_site.occupancy / _atom_site.type_symbol / _chem_comp.formula / _chem_comp.formula_weight / _chem_comp.id / _chem_comp.mon_nstd_flag / _chem_comp.name / _chem_comp.pdbx_synonyms / _chem_comp.type / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _entity_src_gen.gene_src_common_name / _pdbx_struct_assembly.details / _pdbx_struct_assembly.method_details / _pdbx_struct_assembly.oligomeric_count / _pdbx_struct_assembly.oligomeric_details / _pdbx_struct_assembly_gen.asym_id_list / _pdbx_struct_assembly_prop.value / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr2_label_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_special_symmetry.auth_seq_id / _pdbx_struct_special_symmetry.label_asym_id / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_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_comp_id / _struct_conn.ptnr2_label_seq_id / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site_gen.auth_asym_id / _struct_site_gen.auth_comp_id / _struct_site_gen.auth_seq_id / _struct_site_gen.label_asym_id / _struct_site_gen.label_comp_id / _struct_site_gen.label_seq_id
Revision 3.0Nov 15, 2023Group: Atomic model / Data collection / Category: atom_site / chem_comp_atom / chem_comp_bond / Item: _atom_site.auth_atom_id / _atom_site.label_atom_id
Revision 3.1Jan 31, 2024Group: Refinement description / Category: pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Furin
B: 4-guanidinomethyl-phenylacetyl-Arg-Tle-Canavanine-Amba
hetero molecules


Theoretical massNumber of molelcules
Total (without water)53,37212
Polymers52,8792
Non-polymers49310
Water8,359464
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2730 Å2
ΔGint-71 kcal/mol
Surface area17350 Å2
MethodPISA
Unit cell
Length a, b, c (Å)131.785, 131.785, 155.354
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-707-

HOH

31A-1099-

HOH

41A-1156-

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 / Production host: Homo sapiens (human) / References: UniProt: P09958, furin
#2: Protein/peptide 4-guanidinomethyl-phenylacetyl-Arg-Tle-Canavanine-Amba


Mass: 766.917 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others)

-
Non-polymers , 6 types, 474 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.: 3 / 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-PO4 / PHOSPHATE ION


Mass: 94.971 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: PO4
#7: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#8: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 464 / 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: 3.74 Å3/Da / Density % sol: 67.08 %
Crystal growTemperature: 291.15 K / Method: vapor diffusion, sitting drop
Details: CRYSTALLIZATION SOLUTION: 100MM MES, 200MM K/NAH2PO4, PH 5.5-6.0, 2 M NACL; RESERVOIR SOLUTION: 3-4M NACL

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: BESSY / Beamline: 14.2 / Wavelength: 0.9184 Å
DetectorType: DECTRIS PILATUS3 2M / Detector: PIXEL / Date: Oct 11, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9184 Å / Relative weight: 1
ReflectionResolution: 1.8→47.2 Å / Num. obs: 73093 / % possible obs: 98.6 % / Redundancy: 20.2 % / Biso Wilson estimate: 23.6 Å2 / Rrim(I) all: 0.141 / Net I/σ(I): 21.24
Reflection shellResolution: 1.8→1.91 Å / Num. unique obs: 11510 / Rrim(I) all: 1.609

-
Processing

Software
NameVersionClassification
XDSdata reduction
XDSdata scaling
Cootmodel building
PHENIX1.17.1refinement
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5JXH

5jxh


Resolution: 1.8→36.77 Å / SU ML: 0.1662 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 16.5091
RfactorNum. reflection% reflection
Rfree0.1709 3589 4.92 %
Rwork0.1538 --
obs0.1546 72887 98.64 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso mean: 29.7 Å2
Refinement stepCycle: LAST / Resolution: 1.8→36.77 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3608 0 76 464 4148
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00923828
X-RAY DIFFRACTIONf_angle_d0.97935228
X-RAY DIFFRACTIONf_chiral_restr0.0594563
X-RAY DIFFRACTIONf_plane_restr0.0074698
X-RAY DIFFRACTIONf_dihedral_angle_d27.99581404
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.8-1.820.30241600.25242564X-RAY DIFFRACTION97.56
1.82-1.850.23971410.23642582X-RAY DIFFRACTION97.63
1.85-1.880.25041290.21892614X-RAY DIFFRACTION97.82
1.88-1.90.28371380.2132602X-RAY DIFFRACTION97.96
1.9-1.930.22421350.19612594X-RAY DIFFRACTION98.02
1.93-1.960.2311340.17782602X-RAY DIFFRACTION97.75
1.96-20.18681120.17472673X-RAY DIFFRACTION98.13
2-2.030.19421360.16872595X-RAY DIFFRACTION98.31
2.03-2.070.18221310.16072624X-RAY DIFFRACTION98.15
2.07-2.120.16941490.15232599X-RAY DIFFRACTION98.42
2.12-2.160.16021370.14432651X-RAY DIFFRACTION98.45
2.16-2.210.1741400.13642627X-RAY DIFFRACTION98.4
2.21-2.270.1431350.13732639X-RAY DIFFRACTION98.68
2.27-2.330.16071180.14162661X-RAY DIFFRACTION98.62
2.33-2.40.17951240.1392674X-RAY DIFFRACTION98.66
2.4-2.480.14851330.14412654X-RAY DIFFRACTION98.79
2.48-2.560.16251280.1442671X-RAY DIFFRACTION99.01
2.56-2.670.17411250.15372668X-RAY DIFFRACTION99.01
2.67-2.790.18371500.15742688X-RAY DIFFRACTION99.02
2.79-2.930.18331430.16282680X-RAY DIFFRACTION99.12
2.93-3.120.16091340.16052696X-RAY DIFFRACTION99.33
3.12-3.360.18941510.14772716X-RAY DIFFRACTION99.48
3.36-3.70.15191520.13562722X-RAY DIFFRACTION99.48
3.7-4.230.13041470.11752751X-RAY DIFFRACTION99.55
4.23-5.330.12911480.12812794X-RAY DIFFRACTION99.8
5.33-36.770.19281590.19892957X-RAY DIFFRACTION99.27
Refinement TLS params.Method: refined / Origin x: 35.3220792803 Å / Origin y: -37.6591338687 Å / Origin z: 0.262563643938 Å
111213212223313233
T0.134711858892 Å2-0.0131928734116 Å20.0075133306765 Å2-0.189945059404 Å2-0.000967251515831 Å2--0.171361505283 Å2
L0.424238757184 °20.069951265444 °2-0.0233097414788 °2-0.569172479231 °20.247375854297 °2--0.615090272168 °2
S-0.0163316386817 Å °0.0491840919449 Å °-0.0319044358858 Å °-0.062846660897 Å °0.0108197387583 Å °0.022469687792 Å °-0.00431602452135 Å °-0.0834506563364 Å °5.51768134745E-7 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://pdbjlvh1.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