[English] 日本語
Yorodumi
- PDB-1qur: HUMAN ALPHA-THROMBIN IN COMPLEX WITH BIVALENT, BENZAMIDINE-BASED ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 1qur
TitleHUMAN ALPHA-THROMBIN IN COMPLEX WITH BIVALENT, BENZAMIDINE-BASED SYNTHETIC INHIBITOR
Components
  • BIVALENT INHIBITOR (BZA-2 HIRULOG)
  • HUMAN THROMBIN (ALPHA CHAIN)
  • HUMAN THROMBIN (BETA CHAIN)
KeywordsHYDROLASE/HYDROLASE INHIBITOR / TRYPSIN LIKE SERINE PROTEASE / BLOOD COAGULATION / HYDROLASE-HYDROLASE INHIBITOR COMPLEX
Function / homology
Function and homology information


cytolysis by host of symbiont cells / positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway / thrombospondin receptor activity / Defective factor XII causes hereditary angioedema / thrombin-activated receptor signaling pathway / thrombin / neutrophil-mediated killing of gram-negative bacterium / regulation of blood coagulation / Defective F8 cleavage by thrombin / ligand-gated ion channel signaling pathway ...cytolysis by host of symbiont cells / positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway / thrombospondin receptor activity / Defective factor XII causes hereditary angioedema / thrombin-activated receptor signaling pathway / thrombin / neutrophil-mediated killing of gram-negative bacterium / regulation of blood coagulation / Defective F8 cleavage by thrombin / ligand-gated ion channel signaling pathway / Platelet Aggregation (Plug Formation) / negative regulation of astrocyte differentiation / positive regulation of collagen biosynthetic process / negative regulation of platelet activation / negative regulation of blood coagulation / positive regulation of blood coagulation / negative regulation of fibrinolysis / regulation of cytosolic calcium ion concentration / Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus / Gamma-carboxylation of protein precursors / Common Pathway of Fibrin Clot Formation / Removal of aminoterminal propeptides from gamma-carboxylated proteins / fibrinolysis / negative regulation of proteolysis / Intrinsic Pathway of Fibrin Clot Formation / negative regulation of cytokine production involved in inflammatory response / positive regulation of release of sequestered calcium ion into cytosol / Peptide ligand-binding receptors / Regulation of Complement cascade / acute-phase response / positive regulation of receptor signaling pathway via JAK-STAT / Cell surface interactions at the vascular wall / lipopolysaccharide binding / growth factor activity / positive regulation of insulin secretion / platelet activation / positive regulation of protein localization to nucleus / response to wounding / Golgi lumen / antimicrobial humoral immune response mediated by antimicrobial peptide / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / positive regulation of reactive oxygen species metabolic process / blood coagulation / heparin binding / regulation of cell shape / Thrombin signalling through proteinase activated receptors (PARs) / positive regulation of protein phosphorylation / positive regulation of cell growth / : / G alpha (q) signalling events / blood microparticle / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / cell surface receptor signaling pathway / receptor ligand activity / endoplasmic reticulum lumen / signaling receptor binding / serine-type endopeptidase activity / positive regulation of cell population proliferation / calcium ion binding / proteolysis / extracellular space / extracellular exosome / extracellular region / plasma membrane
Similarity search - Function
Prothrombin/thrombin / Thrombin light chain / Thrombin light chain domain superfamily / : / Thrombin light chain / Kringle domain / Kringle / Kringle, conserved site / Kringle superfamily / Kringle domain signature. ...Prothrombin/thrombin / Thrombin light chain / Thrombin light chain domain superfamily / : / Thrombin light chain / Kringle domain / Kringle / Kringle, conserved site / Kringle superfamily / Kringle domain signature. / Kringle domain profile. / Kringle domain / Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain / Gamma-carboxyglutamic acid-rich (GLA) domain / Gamma-carboxyglutamic acid-rich (GLA) domain superfamily / Vitamin K-dependent carboxylation domain. / Gla domain profile. / Domain containing Gla (gamma-carboxyglutamate) residues. / Kringle-like fold / Serine proteases, trypsin family, histidine active site / Serine proteases, trypsin family, serine active site / Serine proteases, trypsin family, histidine active site. / Peptidase S1A, chymotrypsin family / 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
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / Resolution: 2 Å
AuthorsRenatus, M. / Steinmetzer, T.
CitationJournal: Eur.J.Biochem. / Year: 1999
Title: Design and evaluation of novel bivalent thrombin inhibitors based on amidinophenylalanines.
Authors: Steinmetzer, T. / Renatus, M. / Kunzel, S. / Eichinger, A. / Bode, W. / Wikstrom, P. / Hauptmann, J. / Sturzebecher, J.
History
DepositionJul 2, 1999Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 14, 1999Provider: repository / Type: Initial release
Revision 1.1Apr 27, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Atomic model / Database references ...Atomic model / Database references / Derived calculations / Non-polymer description / Structure summary / Version format compliance
Revision 2.0Nov 15, 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_validate_polymer_linkage / struct_conn / struct_ref_seq
Item: _atom_site.auth_atom_id / _atom_site.label_atom_id ..._atom_site.auth_atom_id / _atom_site.label_atom_id / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _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_comp_id / _struct_conn.ptnr2_label_seq_id / _struct_ref_seq.db_align_beg / _struct_ref_seq.db_align_end
Revision 2.1Oct 30, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
L: HUMAN THROMBIN (ALPHA CHAIN)
H: HUMAN THROMBIN (BETA CHAIN)
I: BIVALENT INHIBITOR (BZA-2 HIRULOG)


Theoretical massNumber of molelcules
Total (without water)35,1873
Polymers35,1873
Non-polymers00
Water2,702150
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5570 Å2
ΔGint-5 kcal/mol
Surface area13690 Å2
MethodPISA
Unit cell
Length a, b, c (Å)71.320, 72.410, 72.330
Angle α, β, γ (deg.)90.00, 100.27, 90.00
Int Tables number5
Space group name H-MC121
DetailsThe biological assembly of alpha-thrombin consists of the large and small subunit, linked by a disulfid bridge

-
Components

#1: Protein/peptide HUMAN THROMBIN (ALPHA CHAIN)


Mass: 3188.627 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P00734
#2: Protein HUMAN THROMBIN (BETA CHAIN)


Mass: 29594.055 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P00734
#3: Protein/peptide BIVALENT INHIBITOR (BZA-2 HIRULOG)


Mass: 2404.564 Da / Num. of mol.: 1 / Source method: obtained synthetically
Details: The inhibitor was chemically synthesized AS COMBINATION OF ORGANIC AND SOLID PHASE PEPTIDE SYNTHESIS. THE ACTIVE SITE BINDING PORTION IS DERIVED FROM THE SYNTHETICAL INHIBITOR NAPAP,THE ...Details: The inhibitor was chemically synthesized AS COMBINATION OF ORGANIC AND SOLID PHASE PEPTIDE SYNTHESIS. THE ACTIVE SITE BINDING PORTION IS DERIVED FROM THE SYNTHETICAL INHIBITOR NAPAP,THE SEQUENCE OF THE EXOSITE BINDING PORTION WAS DERIVED FROM THE NATURALLY OCCURING INHIBITOR HIRUDIN, ISOLATED FROM THE MEDICAL LEECH AND THE SYNTHETICALLY SYNTHESIZED EXOSITE INHIBITOR MDL-28,050.
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 150 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.65 Å3/Da / Density % sol: 53.65 %
Crystal growTemperature: 280 K / Method: macro seeding
Details: 100 mM Tris/HCl, 300-500 mM NaCl, 22-32% (w/v) PEG 8000, macro seeding, temperature 280K
Crystal grow
*PLUS
Temperature: 6 ℃ / pH: 6 / Method: vapor diffusion, hanging drop
Components of the solutions
*PLUS
IDConc.Common nameCrystal-IDSol-IDChemical formulaDetails
13 mMHEPES1drop
2150 mM1dropNaCl
422-32 %(w/v)PEG80001reservoir
5300-500 mM1reservoirNaCl
6100 mMTris-HCl1reservoir
3inhibitor1drop20 fold excess ob BZA-2

-
Data collection

DiffractionMean temperature: 290 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU RU300 / Wavelength: 1.5418
DetectorType: MARRESEARCH / Detector: IMAGE PLATE / Date: Nov 23, 1998
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 1.98→9 Å / Num. all: 54304 / Num. obs: 23412 / % possible obs: 93.4 % / Observed criterion σ(F): 2 / Observed criterion σ(I): 2 / Redundancy: 2.3 % / Biso Wilson estimate: 21.604 Å2 / Rmerge(I) obs: 0.128 / Net I/σ(I): 4
Reflection shellResolution: 1.98→2.09 Å / Redundancy: 2 % / Rmerge(I) obs: 0.476 / Mean I/σ(I) obs: 1.2 / % possible all: 82
Reflection shell
*PLUS
% possible obs: 82 %

-
Processing

Software
NameVersionClassification
MOSFLMdata reduction
SCALAdata scaling
CNSrefinement
CCP4(SCALA)data scaling
RefinementResolution: 2→9 Å / Data cutoff high rms absF: 10000 / σ(F): 0 / σ(I): 0 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflectionSelection details
Rfree0.246 23360 5 %RANDOM
Rwork0.209 ---
all-24276 --
obs-23360 96.2 %-
Displacement parameters
Baniso -1Baniso -2Baniso -3
1--0.427 Å20 Å20.764 Å2
2--5.839 Å20 Å2
3----5.412 Å2
Refinement stepCycle: LAST / Resolution: 2→9 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2472 0 0 150 2622
Refine LS restraints
Refine-IDTypeDev idealDev ideal target
X-RAY DIFFRACTIONx_bond_d0.009314
X-RAY DIFFRACTIONx_angle_deg1.5248
X-RAY DIFFRACTIONx_mcbond_it1.4571.5
X-RAY DIFFRACTIONx_mcangle_it2.0862
X-RAY DIFFRACTIONx_scbond_it2.312
X-RAY DIFFRACTIONx_scangle_it3.0822.5
LS refinement shellResolution: 2→2.03 Å / Total num. of bins used: 22 /
RfactorNum. reflection
Rfree0.323 -
Rwork-53
Xplor fileSerial no: 1 / Param file: CNS_TOPPAR:protein_rep.param / Topol file: CNS_TOPPAR:water_rep.param
Software
*PLUS
Name: CNS / Classification: refinement
Refinement
*PLUS
Highest resolution: 2 Å / Lowest resolution: 9 Å / σ(F): 0 / % reflection Rfree: 5 % / Rfactor obs: 0.2085 / Rfactor Rfree: 0.2468
Solvent computation
*PLUS
Displacement parameters
*PLUS
Refine LS restraints
*PLUS
Refine-IDTypeDev ideal target
X-RAY DIFFRACTIONc_bond_d
X-RAY DIFFRACTIONc_angle_deg
X-RAY DIFFRACTIONc_mcbond_it1.5
X-RAY DIFFRACTIONc_scbond_it2
X-RAY DIFFRACTIONc_mcangle_it2
X-RAY DIFFRACTIONc_scangle_it2.5
LS refinement shell
*PLUS
Rfactor Rfree: 0.323

+
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