[English] 日本語
Yorodumi
- PDB-3ig6: Low molecular weigth human Urokinase type Plasminogen activator 2... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3ig6
TitleLow molecular weigth human Urokinase type Plasminogen activator 2-[6-(3'-Aminomethyl-biphenyl-3-yloxy)-4-(3-dimethylamino-pyrrolidin-1-yl)-3,5-difluoro-pyridin-2-yloxy]-4-dimethylamino-benzoic acid complex
Components(Urokinase-type plasminogen activator) x 2
KeywordsHYDROLASE / SELECTIVE / S1 SITE INHIBITOR / STRUCTURE-BASED DRUG DESIGN / UROKINASE / Blood coagulation / Disulfide bond / EGF-like domain / Fibrinolysis / Glycoprotein / Kringle / Pharmaceutical / Phosphoprotein / Plasminogen activation / Polymorphism / Protease / Secreted / Serine protease / Zymogen
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
Chem-438 / PHOSPHATE ION / Urokinase-type plasminogen activator / Urokinase-type plasminogen activator
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.83 Å
AuthorsAdler, M. / Whitlow, M.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2009
Title: Identification of orally bioavailable, non-amidine inhibitors of Urokinase Plasminogen Activator (uPA)
Authors: West, C.W. / Adler, M. / Arnaiz, D. / Chen, D. / Chu, K. / Gualtieri, G. / Ho, E. / Huwe, C. / Light, D. / Phillips, G. / Pulk, R. / Sukovich, D. / Whitlow, M. / Yuan, S. / Bryant, J.
History
DepositionJul 27, 2009Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 13, 2009Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Nov 16, 2011Group: Atomic model
Revision 1.3Sep 6, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Urokinase-type plasminogen activator
B: Urokinase-type plasminogen activator
C: Urokinase-type plasminogen activator
D: Urokinase-type plasminogen activator
hetero molecules


Theoretical massNumber of molelcules
Total (without water)63,6397
Polymers62,3374
Non-polymers1,3023
Water4,089227
1
A: Urokinase-type plasminogen activator
B: Urokinase-type plasminogen activator
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,7723
Polymers31,1692
Non-polymers6041
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
C: Urokinase-type plasminogen activator
D: Urokinase-type plasminogen activator
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,8674
Polymers31,1692
Non-polymers6992
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
A: Urokinase-type plasminogen activator
B: Urokinase-type plasminogen activator
C: Urokinase-type plasminogen activator
D: Urokinase-type plasminogen activator
hetero molecules

A: Urokinase-type plasminogen activator
B: Urokinase-type plasminogen activator
C: Urokinase-type plasminogen activator
D: Urokinase-type plasminogen activator
hetero molecules


Theoretical massNumber of molelcules
Total (without water)127,27914
Polymers124,6748
Non-polymers2,6056
Water1086
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation2_555-x,y,-z1
Buried area11480 Å2
ΔGint-55 kcal/mol
Surface area37020 Å2
MethodPISA
4


  • Idetical with deposited unit
  • defined by software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4080 Å2
ΔGint-22 kcal/mol
Surface area20170 Å2
MethodPISA
Unit cell
Length a, b, c (Å)70.855, 52.294, 72.580
Angle α, β, γ (deg.)90.00, 90.23, 90.00
Int Tables number3
Space group name H-MP121
Components on special symmetry positions
IDModelComponents
11B-839-

HOH

-
Components

#1: Protein/peptide Urokinase-type plasminogen activator / 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: 2708.183 Da / Num. of mol.: 2 / Fragment: FRAGMENT OF LIGHT CHAIN
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PLAU / Production host: Escherichia coli (E. coli)
References: UniProt: Q5SWW9, UniProt: P00749*PLUS, u-plasminogen activator
#2: Protein Urokinase-type plasminogen activator / 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: 28460.412 Da / Num. of mol.: 2 / Fragment: CATALYTIC DOMAIN
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PLAU / Production host: Escherichia coli (E. coli)
References: UniProt: Q5SWW9, UniProt: P00749*PLUS, u-plasminogen activator
#3: Chemical ChemComp-438 / 2-[(6-{[3'-(aminomethyl)biphenyl-3-yl]oxy}-4-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]-3,5-difluoropyridin-2-yl)oxy]-4-(dimethylamino)benzoic acid


Mass: 603.659 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C33H35F2N5O4
#4: Chemical ChemComp-PO4 / PHOSPHATE ION


Mass: 94.971 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: PO4
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 227 / Source method: isolated from a natural source / Formula: H2O
Sequence detailsAUTHORS STATE THAT THE ACTIVE FORM OF UROKINASE IS CREATED BY A PROTEOLYTIC CLIP, THUS IT HAS TWO CHAINS

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.16 Å3/Da / Density % sol: 42.98 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7.4
Details: 20.4 g/l, 1 mM ligand in 50 mM Tris pH 7.4, 5 mM NaCl, VAPOR DIFFUSION, HANGING DROP, temperature 298K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.1 / Wavelength: 1 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 210 / Detector: CCD / Date: Jan 22, 2003
RadiationMonochromator: Single crystal, cylindrically bent, Si(220) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.83→20 Å / Num. all: 48073 / Num. obs: 47497 / % possible obs: 98.8 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 2.45 % / Biso Wilson estimate: 12.4 Å2 / Rsym value: 0.0535 / Net I/σ(I): 15.15
Reflection shellResolution: 1.83→1.94 Å / Redundancy: 2.26 % / Mean I/σ(I) obs: 2.6 / Num. unique all: 5887 / Rsym value: 0.244 / % possible all: 99.4

-
Processing

Software
NameClassification
BOSdata collection
CNXrefinement
XTALVIEWrefinement
X-GENdata reduction
X-GENdata scaling
CNXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1LMW

1lmw


Resolution: 1.83→19.83 Å / Rfactor Rfree error: 0.006 / Data cutoff high absF: 132827.96 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 2 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflectionSelection details
Rfree0.228 1684 3.9 %RANDOM
Rwork0.197 ---
obs0.198 42641 90.4 %-
all-46597 --
Solvent computationSolvent model: FLAT MODEL / Bsol: 50.936 Å2 / ksol: 0.403955 e/Å3
Displacement parametersBiso mean: 22.9 Å2
Baniso -1Baniso -2Baniso -3
1-1.5 Å20 Å24.94 Å2
2--1.59 Å20 Å2
3----3.1 Å2
Refine analyze
FreeObs
Luzzati coordinate error0.24 Å0.2 Å
Luzzati d res low-5 Å
Luzzati sigma a0.18 Å0.12 Å
Refinement stepCycle: LAST / Resolution: 1.83→19.83 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3939 0 93 227 4259
Refine LS restraints
Refine-IDTypeDev idealDev ideal target
X-RAY DIFFRACTIONc_bond_d0.007
X-RAY DIFFRACTIONc_angle_deg1
X-RAY DIFFRACTIONc_dihedral_angle_d22.2
X-RAY DIFFRACTIONc_improper_angle_d0.66
X-RAY DIFFRACTIONc_mcbond_it1.431.5
X-RAY DIFFRACTIONc_mcangle_it2.172
X-RAY DIFFRACTIONc_scbond_it2.622
X-RAY DIFFRACTIONc_scangle_it4.063
Refine LS restraints NCSNCS model details: NONE
LS refinement shellResolution: 1.83→1.94 Å / Rfactor Rfree error: 0.019 / Total num. of bins used: 6
RfactorNum. reflection% reflection
Rfree0.29 232 3.8 %
Rwork0.234 5887 -
obs-5887 78.3 %
Xplor file
Refine-IDSerial noParam fileTopol file
X-RAY DIFFRACTION1protein_rep.pprotein.top
X-RAY DIFFRACTION2water_rep.parwater.top
X-RAY DIFFRACTION3ion.paramion.top
X-RAY DIFFRACTION4438.par438.top
X-RAY DIFFRACTION5&_1_PARAMETER_INFILE_5&_1_TOPOLOGY_INFILE_5

+
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