[English] 日本語
Yorodumi
- PDB-1c5w: STRUCTURAL BASIS FOR SELECTIVITY OF A SMALL MOLECULE, S1-BINDING,... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 1c5w
TitleSTRUCTURAL BASIS FOR SELECTIVITY OF A SMALL MOLECULE, S1-BINDING, SUB-MICROMOLAR INHIBITOR OF UROKINASE TYPE PLASMINOGEN ACTIVATOR
Components(PROTEIN (UROKINASE-TYPE PLASMINOGEN ACTIVATOR)) x 2
KeywordsBLOOD CLOTTING / selective / S1 site inhibitor / structure-based drug design / urokinase / trypsin / thrombin
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 / tertiary granule membrane / regulation of cell adhesion mediated by integrin / negative regulation of fibrinolysis / specific granule membrane / regulation of cell adhesion / 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
4-IODOBENZO[B]THIOPHENE-2-CARBOXAMIDINE / CITRATE ANION / Urokinase-type plasminogen activator
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / DIFFERENCE FOURIER PLUS REFINEMENT / Resolution: 1.94 Å
AuthorsKatz, B.A. / Mackman, R. / Luong, C. / Radika, K. / Martelli, A. / Sprengeler, P.A. / Wang, J. / Chan, H. / Wong, L.
CitationJournal: Chem.Biol. / Year: 2000
Title: Structural basis for selectivity of a small molecule, S1-binding, submicromolar inhibitor of urokinase-type plasminogen activator.
Authors: Katz, B.A. / Mackman, R. / Luong, C. / Radika, K. / Martelli, A. / Sprengeler, P.A. / Wang, J. / Chan, H. / Wong, L.
History
DepositionDec 22, 1999Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 22, 2000Provider: repository / Type: Initial release
Revision 1.1Apr 26, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Version format compliance
Revision 1.3Oct 4, 2017Group: Advisory / Refinement description
Category: pdbx_unobs_or_zero_occ_atoms / pdbx_unobs_or_zero_occ_residues / software
Revision 2.0Dec 27, 2023Group: Advisory / Atomic model ...Advisory / Atomic model / Data collection / Database references / Derived calculations
Category: atom_site / chem_comp_atom ...atom_site / chem_comp_atom / chem_comp_bond / database_2 / pdbx_unobs_or_zero_occ_atoms / pdbx_unobs_or_zero_occ_residues / struct_ref_seq_dif / struct_site
Item: _atom_site.occupancy / _database_2.pdbx_DOI ..._atom_site.occupancy / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 2.1Apr 3, 2024Group: Advisory / Refinement description
Category: pdbx_initial_refinement_model / pdbx_validate_close_contact / pdbx_validate_symm_contact

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: PROTEIN (UROKINASE-TYPE PLASMINOGEN ACTIVATOR)
B: PROTEIN (UROKINASE-TYPE PLASMINOGEN ACTIVATOR)
hetero molecules


Theoretical massNumber of molelcules
Total (without water)32,0146
Polymers31,1442
Non-polymers8704
Water5,296294
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2420 Å2
ΔGint1 kcal/mol
Surface area11480 Å2
MethodPISA
Unit cell
Length a, b, c (Å)82.090, 49.740, 66.470
Angle α, β, γ (deg.)90.00, 113.21, 90.00
Int Tables number5
Space group name H-MC121
Components on special symmetry positions
IDModelComponents
11B-531-

HOH

21B-531-

HOH

31B-532-

HOH

41B-532-

HOH

-
Components

#1: Protein/peptide PROTEIN (UROKINASE-TYPE PLASMINOGEN ACTIVATOR)


Mass: 2708.183 Da / Num. of mol.: 1 / Fragment: SHORT CHAIN
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Plasmid: PPIC9 / Production host: Pichia pastoris (fungus) / Strain (production host): HISTIDINE DEFICIENT GS115 / References: UniProt: P00749, u-plasminogen activator
#2: Protein PROTEIN (UROKINASE-TYPE PLASMINOGEN ACTIVATOR)


Mass: 28435.428 Da / Num. of mol.: 1 / Fragment: CATALYTIC DOMAIN
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Plasmid: PPIC9 / Production host: Pichia pastoris (fungus) / Strain (production host): HISTIDINE DEFICIENT GS115 / References: UniProt: P00749, u-plasminogen activator
#3: Chemical ChemComp-FLC / CITRATE ANION / Citric acid


Mass: 189.100 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C6H5O7
#4: Chemical ChemComp-ESI / 4-IODOBENZO[B]THIOPHENE-2-CARBOXAMIDINE


Mass: 303.143 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C9H8IN2S
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 294 / 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 Å3/Da / Density % sol: 25.6 %
Crystal growpH: 6.5
Details: LMW human uPA/A145 was concentrated to 10 mg/ml and incubated in 50 mM HEPES, 5.0 mM NaCl. pH 7.0, 1.4 mM 4-iodobenzo[b]thiophene-2-carboxamidine for 15 min on ice. The complex was ...Details: LMW human uPA/A145 was concentrated to 10 mg/ml and incubated in 50 mM HEPES, 5.0 mM NaCl. pH 7.0, 1.4 mM 4-iodobenzo[b]thiophene-2-carboxamidine for 15 min on ice. The complex was crystallized by vapor diffusion in hanging drops containing equal volumes of protein-inhibitor solution (0.28 mM uPA/A145, 1.4 mM inhibitor) and well solution (20 % 2-propanol, 20 % PEG 4K, 100 mM sodium citrate, pH 6.5) sealed over the well.

-
Data collection

DiffractionMean temperature: 298 K
Diffraction sourceSource: ROTATING ANODE / Wavelength: 1.5418
DetectorType: RIGAKU RAXIS IV++ / Detector: IMAGE PLATE / Date: Mar 22, 1998 / Details: MSC MIRRORS
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 1.7→41.52 Å / Num. all: 15791 / % possible obs: 79 % / Observed criterion σ(I): 1 / Redundancy: 2.4 % / Rmerge(I) obs: 0.076 / Net I/σ(I): 6.3
Reflection shellResolution: 1.94→2.03 Å / Rmerge(I) obs: 0.195 / Mean I/σ(I) obs: 2.3 / % possible all: 49.5

-
Processing

Software
NameVersionClassification
bioteX(MSC)data collection
bioteX(MSC)data reduction
X-PLOR3.1model building
Quantamodel building
Insight IImodel building
X-PLOR3.1refinement
bioteXdata scaling
X-PLOR3.1phasing
RefinementMethod to determine structure: DIFFERENCE FOURIER PLUS REFINEMENT
Starting model: PDB1LMW

Resolution: 1.94→7.5 Å / Cross valid method: X-PLOR / σ(F): 2
Details: Bulk solvent terms included in Fob file created with standard X-PLOR script. Only Leu A9 to Thr_A17 are included for the A-chain. Residues prior and after these residues are not visible ...Details: Bulk solvent terms included in Fob file created with standard X-PLOR script. Only Leu A9 to Thr_A17 are included for the A-chain. Residues prior and after these residues are not visible (disordered). Residues after Glu_B245 are not visible (disordered). Residues simultaneously refined in two or more conformations are: Ile_B17, Val_B38, Met_B47, Met_B81, Glu_B86, Leu_B123, Thr_B139, Arg_B166, Gln_B192, Lys_B223, Ser_B232 No energy terms between citrate 1 and 2 are included because they appear to be hydrogen-bonded to one another via an unusually short hydrogen bond between carboxylate groups. Disordered waters are: HOH33 which is close to HOH36; HOH303 which is close to HOH306; HOH715 which is close to HOH720; HOH945 which is close to a symmetry-related equivalent of itself; HOH946 which is close to a symmetry-related equivalent of itself; HOH838 which is close to HOH853.
RfactorNum. reflection% reflection
Rfree0.211 1441 10 %
Rwork0.177 --
obs0.177 14228 78.7 %
Refinement stepCycle: LAST / Resolution: 1.94→7.5 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4142 0 75 882 5099
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONx_bond_d0.017
X-RAY DIFFRACTIONx_angle_deg4
X-RAY DIFFRACTIONx_dihedral_angle_d24.4
X-RAY DIFFRACTIONx_improper_angle_d0.44
LS refinement shellResolution: 1.03→1.94 Å / Total num. of bins used: 8
RfactorNum. reflection% reflection
Rfree0.276 119 10 %
Rwork0.27 1002 -
Xplor file
Refine-IDSerial noParam fileTopol file
X-RAY DIFFRACTION1upa6860a_parmallh3x.proupa6860a_topallh6x.pro
X-RAY DIFFRACTION2upa6860a_param11_ucsf.wat

+
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