[English] 日本語
Yorodumi
- PDB-6d40: Highly Potent and Selective Plasmin Inhibitors Based on the Sunfl... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6d40
TitleHighly Potent and Selective Plasmin Inhibitors Based on the Sunflower Trypsin Inhibitor-1 Scaffold Attenuate Fibrinolysis in Plasma
Components
  • PlasminogenPlasmin
  • Trypsin inhibitor 1
KeywordsHYDROLASE / proteases / SFTI / complex / fibrinolysis
Function / homology
Function and homology information


plasmin / trans-synaptic signaling by BDNF, modulating synaptic transmission / trophoblast giant cell differentiation / tissue remodeling / protein antigen binding / tissue regeneration / mononuclear cell migration / negative regulation of cell-cell adhesion mediated by cadherin / Signaling by PDGF / negative regulation of endopeptidase activity ...plasmin / trans-synaptic signaling by BDNF, modulating synaptic transmission / trophoblast giant cell differentiation / tissue remodeling / protein antigen binding / tissue regeneration / mononuclear cell migration / negative regulation of cell-cell adhesion mediated by cadherin / Signaling by PDGF / negative regulation of endopeptidase activity / positive regulation of fibrinolysis / Dissolution of Fibrin Clot / negative regulation of cell-substrate adhesion / myoblast differentiation / biological process involved in interaction with symbiont / labyrinthine layer blood vessel development / muscle cell cellular homeostasis / endopeptidase inhibitor activity / Activation of Matrix Metalloproteinases / apolipoprotein binding / extracellular matrix disassembly / positive regulation of blood vessel endothelial cell migration / negative regulation of fibrinolysis / fibrinolysis / Degradation of the extracellular matrix / serine-type peptidase activity / platelet alpha granule lumen / Schaffer collateral - CA1 synapse / serine-type endopeptidase inhibitor activity / kinase binding / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / blood coagulation / Platelet degranulation / protein-folding chaperone binding / collagen-containing extracellular matrix / blood microparticle / endopeptidase activity / protease binding / protein domain specific binding / negative regulation of cell population proliferation / external side of plasma membrane / signaling receptor binding / serine-type endopeptidase activity / glutamatergic synapse / enzyme binding / cell surface / proteolysis / extracellular space / extracellular exosome / extracellular region / plasma membrane
Similarity search - Function
Peptidase S1A, plasmin / divergent subfamily of APPLE domains / PAN/Apple domain profile. / PAN domain / PAN/Apple domain / Kringle domain / Kringle / Kringle, conserved site / Kringle superfamily / Kringle domain signature. ...Peptidase S1A, plasmin / divergent subfamily of APPLE domains / PAN/Apple domain profile. / PAN domain / PAN/Apple domain / Kringle domain / Kringle / Kringle, conserved site / Kringle superfamily / Kringle domain signature. / Kringle domain profile. / Kringle domain / Kringle-like fold / Serine proteases, trypsin family, histidine active site / Serine proteases, trypsin family, serine active site / Peptidase S1A, chymotrypsin family / Serine proteases, trypsin family, histidine active site. / Serine proteases, trypsin domain profile. / Serine proteases, trypsin family, serine active site. / Trypsin-like serine protease / Serine proteases, trypsin domain / Trypsin / Trypsin-like serine proteases / Thrombin, subunit H / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan / Beta Barrel / Mainly Beta
Similarity search - Domain/homology
Plasminogen / Trypsin inhibitor 1
Similarity search - Component
Biological speciesHomo sapiens (human)
Helianthus annuus (common sunflower)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.43 Å
AuthorsLaw, R.H.P. / Wu, G.
CitationJournal: J. Med. Chem. / Year: 2019
Title: Highly Potent and Selective Plasmin Inhibitors Based on the Sunflower Trypsin Inhibitor-1 Scaffold Attenuate Fibrinolysis in Plasma.
Authors: Swedberg, J.E. / Wu, G. / Mahatmanto, T. / Durek, T. / Caradoc-Davies, T.T. / Whisstock, J.C. / Law, R.H.P. / Craik, D.J.
History
DepositionApr 17, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 23, 2019Provider: repository / Type: Initial release
Revision 1.1May 1, 2019Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.year / _citation_author.name
Revision 1.2Oct 4, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Plasminogen
C: Trypsin inhibitor 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)28,9834
Polymers28,7912
Non-polymers1922
Water3,459192
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1520 Å2
ΔGint-28 kcal/mol
Surface area10650 Å2
MethodPISA
Unit cell
Length a, b, c (Å)85.318, 41.754, 78.996
Angle α, β, γ (deg.)90.000, 109.570, 90.000
Int Tables number5
Space group name H-MC121

-
Components

#1: Protein Plasminogen / Plasmin / microplasmin


Mass: 27193.248 Da / Num. of mol.: 1 / Fragment: UNP residues 563-810
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PLG / Production host: Komagataella pastoris (fungus) / References: UniProt: P00747, plasmin
#2: Protein/peptide Trypsin inhibitor 1 / / SFTI-1


Mass: 1597.899 Da / Num. of mol.: 1 / Fragment: UNP residues 40-53 / Mutation: T4Y / Source method: obtained synthetically / Source: (synth.) Helianthus annuus (common sunflower) / References: UniProt: Q4GWU5
#3: Chemical ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 192 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.3 Å3/Da / Density % sol: 46.58 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 5.5 / Details: 15% PEG4000, 0.1 M MES, 0.15 M ammonium sulfate / PH range: 4.5-6

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Australian Synchrotron / Beamline: MX1 / Wavelength: 0.9537 Å
DetectorType: ADSC QUANTUM 210r / Detector: CCD / Date: Oct 30, 2016
RadiationMonochromator: double crystal Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9537 Å / Relative weight: 1
ReflectionResolution: 1.43→74.434 Å / Num. all: 48727 / Num. obs: 48727 / % possible obs: 100 % / Redundancy: 4.1 % / Biso Wilson estimate: 15.17 Å2 / Rpim(I) all: 0.036 / Rrim(I) all: 0.074 / Rsym value: 0.065 / Net I/av σ(I): 6.7 / Net I/σ(I): 10.4 / Num. measured all: 200154
Reflection shell

Diffraction-ID: 1 / Redundancy: 4.1 %

Resolution (Å)Rmerge(I) obsMean I/σ(I) obsNum. measured allNum. unique obsRpim(I) allRrim(I) allRsym valueNet I/σ(I) obs% possible all
1.43-1.510.6281.22873870580.3550.7240.6282100
1.51-1.60.3891.92739367020.220.4480.3893100
1.6-1.710.24732586762940.1390.2840.2474.4100
1.71-1.850.1524.82419158750.0850.1740.1526.6100
1.85-2.020.097.92237354030.050.1030.0910.5100
2.02-2.260.06610.32030049050.0360.0750.06614.6100
2.26-2.610.06310.41792643290.0340.0720.06317.4100
2.61-3.20.05411.61505836760.030.0620.05421.5100
3.2-4.520.04114.61165628570.0230.0470.04127100
4.52-40.1950.04213.2665216280.0230.0480.04227.599.9

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassificationNB
PHENIX1.13_2998refinement
XDSdata reduction
SCALA3.3.22data scaling
PHASERphasing
PDB_EXTRACT3.24data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entries 5UGG & 1SFI

5ugg

1sfi


Resolution: 1.43→40.195 Å / SU ML: 0.16 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 21.97 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.21 2405 4.94 %
Rwork0.1856 46311 -
obs0.1868 48716 99.98 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 70.67 Å2 / Biso mean: 24.9964 Å2 / Biso min: 9.64 Å2
Refinement stepCycle: final / Resolution: 1.43→40.195 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1972 0 10 197 2179
Biso mean--53.24 32.6 -
Num. residues----260
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 17 / % reflection obs: 100 %

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all
1.43-1.45920.32561470.299427132860
1.4592-1.49090.28511260.277927552881
1.4909-1.52560.27651330.247426812814
1.5256-1.56380.27081360.236626762812
1.5638-1.6060.22611400.219127232863
1.606-1.65330.24331260.213527312857
1.6533-1.70670.21031570.210626912848
1.7067-1.76770.21251500.195426922842
1.7677-1.83840.22621450.198827092854
1.8384-1.92210.20141520.182627002852
1.9221-2.02340.21671360.183827332869
2.0234-2.15020.18851330.175627182851
2.1502-2.31620.20481410.176427432884
2.3162-2.54930.21731600.190727052865
2.5493-2.91810.22451380.182527382876
2.9181-3.67610.20241390.178327642903
3.6761-40.21110.17941460.156128392985
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
11.38851.05510.35764.6291.60324.56850.03260.3582-0.0982-0.413-0.0286-0.18360.34580.0462-0.00450.169-0.04160.04940.2773-0.00590.138257.419512.799581.4603
22.9468-0.082-0.19431.9493-0.44412.803-0.02650.07940.42770.16070.15990.1214-0.3828-0.4425-0.07580.15480.03640.03120.16550.02220.158346.417521.730891.5498
31.8976-0.19310.26671.8127-0.63643.832-0.01820.0094-0.16640.17370.0559-0.13660.30340.0522-0.01160.1525-0.0029-0.00160.0801-0.01220.125454.819.481896.8885
42.8716-0.0496-0.4680.66350.00030.0858-0.1025-0.66660.12970.713-0.06030.0298-0.4593-0.08580.09590.54920.0328-0.06670.2541-0.04610.199854.357718.7794109.7924
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 544 through 565 )A544 - 565
2X-RAY DIFFRACTION2chain 'A' and (resid 566 through 640 )A566 - 640
3X-RAY DIFFRACTION3chain 'A' and (resid 641 through 791 )A641 - 791
4X-RAY DIFFRACTION4chain 'C' and (resid 1 through 14 )C1 - 14

+
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