[English] 日本語
Yorodumi
- PDB-4jk5: Human urokinase-type Plasminogen Activator (uPA) in complex with ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4jk5
TitleHuman urokinase-type Plasminogen Activator (uPA) in complex with a bicyclic peptide inhibitor (UK18-D-Ser)
Components
  • Urokinase-type plasminogen activatorUrokinase
  • bicyclic peptide UK18-D-Ser, uPA inhibitor
KeywordsHYDROLASE/HYDROLASE INHIBITOR / serine protease / chymotrypsin fold / urokinase-type plasminogen activator / bicyclic peptide inhibitor / D-amino acid / HYDROLASE-HYDROLASE INHIBITOR complex
Function / homology
Function and homology information


u-plasminogen activator / regulation of smooth muscle cell-matrix adhesion / urokinase plasminogen activator signaling pathway / regulation of plasminogen activation / regulation of fibrinolysis / regulation of wound healing / protein complex involved in cell-matrix adhesion / negative regulation of plasminogen activation / regulation of smooth muscle cell migration / regulation of signaling receptor activity ...u-plasminogen activator / regulation of smooth muscle cell-matrix adhesion / urokinase plasminogen activator signaling pathway / regulation of plasminogen activation / regulation of fibrinolysis / regulation of wound healing / protein complex involved in cell-matrix adhesion / negative regulation of plasminogen activation / regulation of smooth muscle cell migration / regulation of signaling receptor activity / serine-type endopeptidase complex / Dissolution of Fibrin Clot / smooth muscle cell migration / plasminogen activation / regulation of cell adhesion mediated by integrin / tertiary granule membrane / negative regulation of fibrinolysis / regulation of cell adhesion / specific granule membrane / serine protease inhibitor complex / fibrinolysis / chemotaxis / blood coagulation / regulation of cell population proliferation / response to hypoxia / positive regulation of cell migration / external side of plasma membrane / serine-type endopeptidase activity / focal adhesion / Neutrophil degranulation / cell surface / signal transduction / proteolysis / extracellular space / extracellular exosome / extracellular region / plasma membrane
Similarity search - Function
Kringle domain / Kringle / Kringle, conserved site / Kringle superfamily / Kringle domain signature. / Kringle domain profile. / Kringle domain / Kringle-like fold / EGF-like domain profile. / EGF-like domain signature 1. ...Kringle domain / Kringle / Kringle, conserved site / Kringle superfamily / Kringle domain signature. / Kringle domain profile. / Kringle domain / Kringle-like fold / EGF-like domain profile. / EGF-like domain signature 1. / EGF-like domain / 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
bicyclic peptide UK18-D-Ser / 1,3,5-tris(bromomethyl)benzene / Urokinase-type plasminogen activator
Similarity search - Component
Biological speciesHomo sapiens (human)
Synthetic construct (others)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.55 Å
AuthorsButh, S.A. / Leiman, P.G. / Chen, S. / Heinis, C.
CitationJournal: Chembiochem / Year: 2013
Title: Improving binding affinity and stability of Peptide ligands by substituting glycines with d-amino acids.
Authors: Chen, S. / Gfeller, D. / Buth, S.A. / Michielin, O. / Leiman, P.G. / Heinis, C.
History
DepositionMar 9, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 17, 2013Provider: repository / Type: Initial release
Revision 1.1Jul 31, 2013Group: Database references
Revision 1.2Nov 15, 2017Group: Refinement description / Category: software
Revision 1.3Jun 2, 2021Group: Database references / Derived calculations / Source and taxonomy
Category: entity_src_gen / struct_conn ...entity_src_gen / struct_conn / struct_ref_seq_dif / struct_site
Item: _entity_src_gen.host_org_common_name / _entity_src_gen.pdbx_host_org_cell_line ..._entity_src_gen.host_org_common_name / _entity_src_gen.pdbx_host_org_cell_line / _entity_src_gen.pdbx_host_org_strain / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.pdbx_value_order / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_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_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.4Sep 20, 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: Urokinase-type plasminogen activator
B: bicyclic peptide UK18-D-Ser, uPA inhibitor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)30,50210
Polymers29,4072
Non-polymers1,0948
Water1,874104
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3080 Å2
ΔGint-78 kcal/mol
Surface area11760 Å2
MethodPISA
Unit cell
Length a, b, c (Å)121.239, 121.239, 42.631
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number146
Space group name H-MH3

-
Components

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

#1: Protein Urokinase-type plasminogen activator / Urokinase / U-plasminogen activator / uPA / Urokinase-type plasminogen activator long chain A / Urokinase-type ...U-plasminogen activator / uPA / Urokinase-type plasminogen activator long chain A / Urokinase-type plasminogen activator short chain A / Urokinase-type plasminogen activator chain B


Mass: 27586.420 Da / Num. of mol.: 1 / Fragment: Catalytic domain / Mutation: C122A, N145Q
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Strain: 9606 / Gene: PLAU / Plasmid: pSecTagA / Cell line (production host): HEK-293 / Production host: Homo sapiens (human) / References: UniProt: P00749, u-plasminogen activator
#2: Protein/peptide bicyclic peptide UK18-D-Ser, uPA inhibitor


Type: Cyclic peptide / Class: Inhibitor / Mass: 1821.031 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Synthetic construct (others) / References: bicyclic peptide UK18-D-Ser

-
Non-polymers , 5 types, 112 molecules

#3: Chemical
ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: SO4
#4: Chemical ChemComp-CL / CHLORIDE ION / Chloride


Mass: 35.453 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Cl
#5: Chemical ChemComp-P6G / HEXAETHYLENE GLYCOL / POLYETHYLENE GLYCOL PEG400 / Polyethylene glycol


Mass: 282.331 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C12H26O7 / Comment: precipitant*YM
#6: Chemical ChemComp-ZBR / 1,3,5-tris(bromomethyl)benzene


Type: Cyclic peptide / Class: Inhibitor / Mass: 356.880 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C9H9Br3 / References: bicyclic peptide UK18-D-Ser
#7: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 104 / 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: 2.05 Å3/Da / Density % sol: 40.01 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 4.9
Details: 50mM Na3(cit) pH 4.9, 5% v/v PEG400, 1.8M (NH4)2SO4, 0.05% NaN3, VAPOR DIFFUSION, HANGING DROP, temperature 293K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06DA / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Jun 1, 2012 / Details: mirrors
RadiationMonochromator: Bartels Monochromator with dual channel cut crystals (DCCM) in (+--+) geometry and a toroidal mirror (M2)
Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.55→33.09 Å / Num. all: 33910 / Num. obs: 33907 / % possible obs: 99.9 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 2 / Redundancy: 4.7 % / Biso Wilson estimate: 18.94 Å2 / Rmerge(I) obs: 0.037 / Rsym value: 0.019 / Net I/σ(I): 17.6
Reflection shellResolution: 1.55→1.58 Å / Redundancy: 4.5 % / Rmerge(I) obs: 0.416 / Mean I/σ(I) obs: 3.5 / Num. unique all: 7729 / Rsym value: 0.217 / % possible all: 99.4

-
Processing

Software
NameVersionClassification
PHASERphasing
REFMAC5.7.0032refinement
MOSFLMdata reduction
SCALAdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 2NWN

2nwn


Resolution: 1.55→33.09 Å / Cor.coef. Fo:Fc: 0.98 / Cor.coef. Fo:Fc free: 0.961 / SU B: 5.008 / SU ML: 0.079 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.098 / ESU R Free: 0.089 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.21283 1719 5.1 %RANDOM
Rwork0.14236 ---
all0.14609 33910 --
obs0.14609 32177 99.91 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 35.459 Å2
Baniso -1Baniso -2Baniso -3
1--0.1 Å2-0.1 Å20 Å2
2---0.1 Å2-0 Å2
3---0.33 Å2
Refinement stepCycle: LAST / Resolution: 1.55→33.09 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2058 0 50 104 2212
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0180.0192206
X-RAY DIFFRACTIONr_bond_other_d0.0010.022035
X-RAY DIFFRACTIONr_angle_refined_deg1.9831.9672992
X-RAY DIFFRACTIONr_angle_other_deg0.9293.0064683
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.7385270
X-RAY DIFFRACTIONr_dihedral_angle_2_deg31.87522.70896
X-RAY DIFFRACTIONr_dihedral_angle_3_deg17.14615366
X-RAY DIFFRACTIONr_dihedral_angle_4_deg21.5281518
X-RAY DIFFRACTIONr_chiral_restr0.120.2316
X-RAY DIFFRACTIONr_gen_planes_refined0.0090.0212471
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02518
X-RAY DIFFRACTIONr_rigid_bond_restr5.96134241
X-RAY DIFFRACTIONr_sphericity_free32.22534
X-RAY DIFFRACTIONr_sphericity_bonded27.60754256
LS refinement shellResolution: 1.55→1.59 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.312 131 -
Rwork0.192 2363 -
obs-2494 99.2 %

+
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