[English] 日本語
Yorodumi
- PDB-1wbg: Active site thrombin inhibitors -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 1wbg
TitleActive site thrombin inhibitors
Components
  • HIRUGEN
  • THROMBIN HEAVY CHAIN
  • THROMBIN LIGHT CHAIN
KeywordsHYDROLASE/HYDROLASE INHIBITOR / BLOOD COAGULATION-INHIBITOR / SERINE PROTEASE / BLOOD COAGULATION / ACUTE PHASE / CALCIUM-BINDING / DISEASE MUTATION / GAMMA-CARBOXYGLUTAMIC ACID / GLYCOPROTEIN / KRINGLE / POLYMORPHISME / VITAMIN K / ZYMOGEN / SULFATION / HYDROLASE-HYDROLASE INHIBITOR COMPLEX
Function / homology
Function and homology information


cytolysis by host of symbiont cells / thrombospondin receptor activity / thrombin-activated receptor signaling pathway / Defective factor XII causes hereditary angioedema / thrombin / negative regulation of astrocyte differentiation / regulation of blood coagulation / positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway / neutrophil-mediated killing of gram-negative bacterium / Defective F8 cleavage by thrombin ...cytolysis by host of symbiont cells / thrombospondin receptor activity / thrombin-activated receptor signaling pathway / Defective factor XII causes hereditary angioedema / thrombin / negative regulation of astrocyte differentiation / regulation of blood coagulation / positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway / neutrophil-mediated killing of gram-negative bacterium / Defective F8 cleavage by thrombin / Platelet Aggregation (Plug Formation) / ligand-gated ion channel signaling pathway / negative regulation of platelet activation / positive regulation of collagen biosynthetic process / 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 / Intrinsic Pathway of Fibrin Clot Formation / negative regulation of proteolysis / 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 / Cell surface interactions at the vascular wall / positive regulation of receptor signaling pathway via JAK-STAT / lipopolysaccharide binding / growth factor activity / serine-type endopeptidase inhibitor activity / positive regulation of insulin secretion / platelet activation / response to wounding / positive regulation of protein localization to nucleus / Golgi lumen / 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 / antimicrobial humoral immune response mediated by antimicrobial peptide / blood coagulation / regulation of cell shape / heparin binding / Thrombin signalling through proteinase activated receptors (PARs) / positive regulation of cell growth / : / blood microparticle / G alpha (q) signalling events / cell surface receptor signaling pathway / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / 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
Hirudin / Proteinase inhibitor I14, hirudin / Thrombin inhibitor hirudin / Hirudin/antistatin / Prothrombin/thrombin / Thrombin light chain / Thrombin light chain domain superfamily / : / Thrombin light chain / Kringle domain ...Hirudin / Proteinase inhibitor I14, hirudin / Thrombin inhibitor hirudin / Hirudin/antistatin / 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
Chem-L03 / Prothrombin / Hirudin variant-2
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
HIRUDO MEDICINALIS (medicinal leech)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.2 Å
AuthorsHartshorn, M.J. / Murray, C.W. / Cleasby, A. / Frederickson, M. / Tickle, I.J. / Jhoti, H.
CitationJournal: J.Med.Chem. / Year: 2005
Title: Fragment-Based Lead Discovery Using X-Ray Crystallography
Authors: Hartshorn, M.J. / Murray, C.W. / Cleasby, A. / Frederickson, M. / Tickle, I.J. / Jhoti, H.
History
DepositionNov 1, 2004Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jan 27, 2005Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Atomic model / Database references ...Atomic model / Database references / Derived calculations / Non-polymer description / Structure summary / Version format compliance
Revision 1.2Jun 28, 2017Group: Data collection / Category: diffrn_source / Item: _diffrn_source.type
Revision 1.3Dec 13, 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_conn / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_conn.pdbx_leaving_atom_flag / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.4Oct 23, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification
Remark 700 SHEET DETERMINATION METHOD: DSSP THE SHEETS PRESENTED AS "BB" IN EACH CHAIN ON SHEET RECORDS BELOW ... SHEET DETERMINATION METHOD: DSSP THE SHEETS PRESENTED AS "BB" IN EACH CHAIN ON SHEET RECORDS BELOW IS ACTUALLY AN 6-STRANDED BARREL THIS IS REPRESENTED BY A 7-STRANDED SHEET IN WHICH THE FIRST AND LAST STRANDS ARE IDENTICAL.

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: THROMBIN LIGHT CHAIN
B: THROMBIN HEAVY CHAIN
I: HIRUGEN
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,7007
Polymers35,2403
Non-polymers4604
Water6,990388
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPQS
Unit cell
Length a, b, c (Å)69.392, 71.785, 71.733
Angle α, β, γ (deg.)90.00, 99.87, 90.00
Int Tables number5
Space group name H-MC121
Components on special symmetry positions
IDModelComponents
11B-2144-

HOH

-
Components

-
Protein/peptide , 2 types, 2 molecules AI

#1: Protein/peptide THROMBIN LIGHT CHAIN / THROMBIN / COAGULATION FACTOR II


Mass: 4096.534 Da / Num. of mol.: 1 / Fragment: FRAGMENT ALPHA THROMBIN, RESIDUES 328-363 / Source method: isolated from a natural source / Source: (natural) HOMO SAPIENS (human) / Tissue: BLOOD PLASMA / References: UniProt: P00734, thrombin
#3: Protein/peptide HIRUGEN


Mass: 1363.399 Da / Num. of mol.: 1 / Fragment: PEPTIDE FRAGMENT OF HIRUGEN, RESIDUES 62-71 / Source method: obtained synthetically / Source: (synth.) HIRUDO MEDICINALIS (medicinal leech) / References: UniProt: P09945

-
Protein , 1 types, 1 molecules B

#2: Protein THROMBIN HEAVY CHAIN / THROMBIN / COAGULATION FACTOR II


Mass: 29780.219 Da / Num. of mol.: 1 / Fragment: FRAGMENT ALPHA THROMBIN, RESIDUES 364-622 / Source method: isolated from a natural source / Source: (natural) HOMO SAPIENS (human) / Tissue: BLOOD PLASMA / References: UniProt: P00734, thrombin

-
Non-polymers , 3 types, 392 molecules

#4: Chemical ChemComp-L03 / 3-(4-CHLOROPHENYL)-5-(METHYLTHIO)-4H-1,2,4-TRIAZOLE


Mass: 225.698 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C9H8ClN3S
#5: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 388 / Source method: isolated from a natural source / Formula: H2O

-
Details

Compound detailsFUNCTION: THROMBIN, WHICH CLEAVES BONDS AFTER ARG AND LYS, CONVERTS FIBRINOGEN TO FIBRIN AND ...FUNCTION: THROMBIN, WHICH CLEAVES BONDS AFTER ARG AND LYS, CONVERTS FIBRINOGEN TO FIBRIN AND ACTIVATES FACTORS V, VII, VIII, XIII, AND, IN COMPLEX WITH THROMBOMODULIN, PROTEIN C. CATALYTIC ACTIVITY: PREFERENTIAL CLEAVAGE: ARG-|-GLY; ACTIVATES FIBRINOGEN TO FIBRIN AND RELEASES FIBRINOPEPTIDE A AND B. SUBCELLULAR LOCATION: EXTRACELLULAR. TISSUE SPECIFICITY: EXPRESSED BY THE LIVER AND SECRETED IN PLASMA. DISEASE: DEFECTS IN F2 ARE THE CAUSE OF VARIOUS FORMS OF DYSPROTHROMBINEMIA [MIM:176930]. SIMILARITY: BELONGS TO THE PEPTIDASE S1 FAMILY. SIMILARITY: CONTAINS 1 GAMMA-CARBOXY-GLUTAMATE DOMAIN (GLA) DOMAIN. SIMILARITY: CONTAINS 2 KRINGLE DOMAINS. FUNCTION: HIRUDIN IS A POTENT THROMBIN-SPECIFIC PROTEASE INHIBITOR. IT FORMS A STABLE NON-COVALENT COMPLEX WITH ALPHA- THROMBIN, THEREBY ABOLISHING ITS ABILITY TO CLEAVE FIBRINOGEN. SUBCELLULAR LOCATION: SECRETED.
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.5 Å3/Da / Density % sol: 50.75 %
Crystal growpH: 7.5 / Details: PH 7.50

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU RUH3R / Wavelength: 1.54
DetectorType: RIGAKU CCD / Detector: CCD / Date: Dec 4, 2002 / Details: CONFOCAL MULTILAYER
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54 Å / Relative weight: 1
ReflectionResolution: 2.2→27 Å / Num. obs: 17712 / % possible obs: 97.6 % / Redundancy: 2.04 % / Rmerge(I) obs: 0.07 / Net I/σ(I): 10.1
Reflection shellResolution: 2.2→2.28 Å / Redundancy: 1.85 % / Rmerge(I) obs: 0.23 / Mean I/σ(I) obs: 3.6 / % possible all: 95.4

-
Processing

Software
NameVersionClassification
REFMAC5.2.0005refinement
d*TREKdata reduction
d*TREKdata scaling
IN-HOUSESOFTWAREphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1QJ1

1qj1


Resolution: 2.2→27.21 Å / Cor.coef. Fo:Fc: 0.957 / Cor.coef. Fo:Fc free: 0.895 / SU B: 5.98 / SU ML: 0.154 / Cross valid method: THROUGHOUT / ESU R: 0.272 / ESU R Free: 0.247 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS. DISORDER AT TWO-FOLD; ARG B 75 CLASHES. THE OCCUPANCY OF SIDE CHAIN ATOMS WAS SET TO 0 FOR REFINEMENT. THESE ATOMS REMOVED FOR DURING PDB ANNOTATION.
RfactorNum. reflection% reflectionSelection details
Rfree0.265 876 5.1 %RANDOM
Rwork0.166 ---
obs0.171 16409 97.6 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 22.71 Å2
Baniso -1Baniso -2Baniso -3
1-1.22 Å20 Å2-0.38 Å2
2---1.47 Å20 Å2
3---0.11 Å2
Refinement stepCycle: LAST / Resolution: 2.2→27.21 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2369 0 26 388 2783
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0120.0222452
X-RAY DIFFRACTIONr_bond_other_d0.0040.022193
X-RAY DIFFRACTIONr_angle_refined_deg1.431.9663308
X-RAY DIFFRACTIONr_angle_other_deg0.80835109
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.8635287
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.61623.729118
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.83115431
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.1861519
X-RAY DIFFRACTIONr_chiral_restr0.0890.2337
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.022682
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02500
X-RAY DIFFRACTIONr_nbd_refined0.2130.2501
X-RAY DIFFRACTIONr_nbd_other0.1870.22343
X-RAY DIFFRACTIONr_nbtor_refined0.180.21160
X-RAY DIFFRACTIONr_nbtor_other0.0850.21352
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1440.2108
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.150.27
X-RAY DIFFRACTIONr_symmetry_vdw_other0.2750.251
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.1040.28
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it3.251880
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it3.71962339
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it3.49561210
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it4.4987.5969
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.2→2.26 Å / Total num. of bins used: 20 /
RfactorNum. reflection
Rfree0.356 65
Rwork0.186 1169

+
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