[English] 日本語
Yorodumi
- PDB-4mnw: Crystal structure of urokinase-type plasminogen activator (uPA) c... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4mnw
TitleCrystal structure of urokinase-type plasminogen activator (uPA) complexed with bicyclic peptide UK749
Components
  • Urokinase-type plasminogen activator chain B
  • bicyclic peptide UK749
KeywordsHYDROLASE/HYDROLASE INHIBITOR / competitive inhibitor / bicyclic peptide / inhibitor / protease / 1 / 3 / 5-tris(bromomethyl)benzene (TBMB) cyclization / extracellular / 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. ...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 family, serine active site. / Serine proteases, trypsin domain profile. / 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 UK749 / ACETATE ION / 1,3,5-tris(bromomethyl)benzene / Urokinase-type plasminogen activator
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.49 Å
AuthorsChen, S. / Pojer, F. / Heinis, C.
CitationJournal: Angew.Chem.Int.Ed.Engl. / Year: 2014
Title: Peptide ligands stabilized by small molecules.
Authors: Chen, S. / Bertoldo, D. / Angelini, A. / Pojer, F. / Heinis, C.
History
DepositionSep 11, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 5, 2014Provider: repository / Type: Initial release
Revision 1.1Feb 26, 2014Group: Database references
Revision 1.2Nov 15, 2017Group: Refinement description / Category: software

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Urokinase-type plasminogen activator chain B
B: bicyclic peptide UK749
hetero molecules


Theoretical massNumber of molelcules
Total (without water)30,26811
Polymers29,1992
Non-polymers1,0699
Water3,045169
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3160 Å2
ΔGint-30 kcal/mol
Surface area11850 Å2
MethodPISA
Unit cell
Length a, b, c (Å)52.570, 53.960, 80.170
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

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

#1: Protein Urokinase-type plasminogen activator chain B / U-plasminogen activator / uPA


Mass: 27586.420 Da / Num. of mol.: 1 / Fragment: catalytic domain (UNP residues 179-423) / Mutation: C122A, N145Q
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / 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 UK749


Type: Cyclic peptide / Class: Inhibitor / Mass: 1612.816 Da / Num. of mol.: 1 / Source method: obtained synthetically
Details: modified with 1,3,5-tris(bromomethyl)benzene (TBMB)
References: bicyclic peptide UK749

-
Non-polymers , 5 types, 178 molecules

#3: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4
#4: Chemical
ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: C3H8O3
#5: Chemical ChemComp-ACT / ACETATE ION


Mass: 59.044 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H3O2
#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 UK749
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 169 / 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: 1.95 Å3/Da / Density % sol: 36.83 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop / pH: 4.5
Details: 22% PEG4000, 15% glycerol, 0.17 M ammonium sulfate, 0.1 M sodium acetate, pH 4.5, VAPOR DIFFUSION, HANGING DROP, temperature 291K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 Å
DetectorType: PSI PILATUS 6M / Detector: PIXEL / Date: Dec 16, 2012
RadiationMonochromator: LN2 cooled fixed-exit Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.49→44.76 Å / Num. all: 37488 / Num. obs: 36626 / % possible obs: 97.7 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 3.8 % / Biso Wilson estimate: 14.7 Å2 / Rmerge(I) obs: 0.132 / Net I/σ(I): 8.1
Reflection shellResolution: 1.49→1.57 Å / Redundancy: 3.8 % / Rmerge(I) obs: 0.183 / Mean I/σ(I) obs: 5.7 / Num. unique all: 5394 / % possible all: 98.4

-
Processing

Software
NameVersionClassification
PHASERphasing
REFMAC5.7.0029refinement
MOSFLMdata reduction
SCALAdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.49→43.96 Å / Cor.coef. Fo:Fc: 0.969 / Cor.coef. Fo:Fc free: 0.968 / SU B: 2.14 / SU ML: 0.037 / Cross valid method: THROUGHOUT / σ(F): 1 / ESU R: 0.094 / ESU R Free: 0.067 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.17111 1811 4.9 %RANDOM
Rwork0.15469 ---
obs0.15554 34787 95.41 %-
all-37488 --
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 19.843 Å2
Baniso -1Baniso -2Baniso -3
1--0.03 Å20 Å2-0 Å2
2--1.71 Å20 Å2
3----1.67 Å2
Refinement stepCycle: LAST / Resolution: 1.49→43.96 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2044 0 53 169 2266
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0050.0192153
X-RAY DIFFRACTIONr_bond_other_d0.0010.021990
X-RAY DIFFRACTIONr_angle_refined_deg1.1641.9622913
X-RAY DIFFRACTIONr_angle_other_deg1.9043.0064573
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.0595258
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.56923.33396
X-RAY DIFFRACTIONr_dihedral_angle_3_deg12.11515357
X-RAY DIFFRACTIONr_dihedral_angle_4_deg11.1871515
X-RAY DIFFRACTIONr_chiral_restr0.070.2310
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.0212398
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02504
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr5.0134143
X-RAY DIFFRACTIONr_sphericity_free26.885552
X-RAY DIFFRACTIONr_sphericity_bonded7.76154209
LS refinement shellResolution: 1.49→1.524 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.175 126 -
Rwork0.149 2597 -
obs--98.09 %

+
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