[English] 日本語
Yorodumi
- PDB-2cf8: Complex of recombinant human thrombin with an inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2cf8
TitleComplex of recombinant human thrombin with an inhibitor
Components
  • HIRUDIN IIIA
  • THROMBIN HEAVY CHAIN
  • THROMBIN LIGHT CHAIN
KeywordsHYDROLASE/HYDROLASE INHIBITOR / HYDROLASE/INHIBITOR / ACUTE PHASE / BLOOD COAGULATION / CALCIUM-BINDING / GLYCOPROTEIN / HYDOLASE / SERINE PROTEASE / SERINE PROTEASE INHIBITOR COMPLEX / COMPLEX HYDROLASE-INHIBITOR / HYDROLASE-HYDROLASE INHIBITOR COMPLEX
Function / homology
Function and homology information


positive regulation of lipid kinase activity / positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway / cytolysis by host of symbiont cells / thrombospondin receptor activity / Defective factor XII causes hereditary angioedema / thrombin / neutrophil-mediated killing of gram-negative bacterium / regulation of blood coagulation / ligand-gated ion channel signaling pathway / Defective F8 cleavage by thrombin ...positive regulation of lipid kinase activity / positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway / cytolysis by host of symbiont cells / thrombospondin receptor activity / Defective factor XII causes hereditary angioedema / thrombin / neutrophil-mediated killing of gram-negative bacterium / regulation of blood coagulation / ligand-gated ion channel signaling pathway / Defective F8 cleavage by thrombin / Platelet Aggregation (Plug Formation) / negative regulation of platelet activation / negative regulation of astrocyte differentiation / positive regulation of collagen biosynthetic process / negative regulation of cytokine production involved in inflammatory response / positive regulation of blood coagulation / negative regulation of fibrinolysis / Gamma-carboxylation of protein precursors / Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus / Common Pathway of Fibrin Clot Formation / Removal of aminoterminal propeptides from gamma-carboxylated proteins / regulation of cytosolic calcium ion concentration / fibrinolysis / Intrinsic Pathway of Fibrin Clot Formation / Peptide ligand-binding receptors / positive regulation of release of sequestered calcium ion into cytosol / Regulation of Complement cascade / acute-phase response / lipopolysaccharide binding / Cell surface interactions at the vascular wall / negative regulation of proteolysis / positive regulation of receptor signaling pathway via JAK-STAT / growth factor activity / serine-type endopeptidase inhibitor activity / positive regulation of insulin secretion / response to wounding / platelet activation / Golgi lumen / positive regulation of protein localization to nucleus / 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 / antimicrobial humoral immune response mediated by antimicrobial peptide / Thrombin signalling through proteinase activated receptors (PARs) / heparin binding / regulation of cell shape / G alpha (q) signalling events / positive regulation of cell growth / collagen-containing extracellular matrix / blood microparticle / cell surface receptor signaling pathway / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / G protein-coupled receptor signaling pathway / positive regulation of protein phosphorylation / endoplasmic reticulum lumen / signaling receptor binding / serine-type endopeptidase activity / calcium ion binding / positive regulation of cell population proliferation / proteolysis / extracellular space / extracellular exosome / extracellular region / plasma membrane
Similarity search - Function
Thrombin inhibitor hirudin / Hirudin / Proteinase inhibitor I14, hirudin / Hirudin/antistatin / Prothrombin/thrombin / Thrombin light chain / Thrombin light chain domain superfamily / Thrombin light chain / Kringle domain / Kringle ...Thrombin inhibitor hirudin / Hirudin / Proteinase inhibitor I14, 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 / Peptidase S1A, chymotrypsin family / Serine proteases, trypsin family, histidine active site. / Serine proteases, trypsin domain profile. / Trypsin-like serine protease / Serine proteases, trypsin family, serine active site. / 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
N-terminal Asp des-amino Hirudin-3A / Chem-ESH / Prothrombin / Hirudin-3A'
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
HIRUDO MEDICINALIS (medicinal leech)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 1.3 Å
AuthorsSchweizer, E. / Hoffmann-Roeder, A. / Olsen, J.A. / Obst-Sander, U. / Wagner, B. / Kansy, M. / Banner, D.W. / Diederich, F.
CitationJournal: Org.Biomol.Chem. / Year: 2006
Title: Multipolar Interactions in the D Pocket of Thrombin: Large Differences between Tricyclic Imide and Lactam Inhibitors.
Authors: Schweizer, E. / Hoffmann-Roeder, A. / Olsen, J.A. / Seiler, P. / Obst-Sander, U. / Wagner, B. / Kansy, M. / Banner, D.W. / Diederich, F.
History
DepositionFeb 17, 2006Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jun 14, 2006Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Advisory / Atomic model ...Advisory / Atomic model / Database references / Derived calculations / Non-polymer description / Structure summary / Version format compliance
Revision 1.2Dec 12, 2012Group: Other
Revision 1.3Aug 7, 2013Group: Derived calculations / Other
Revision 1.4Oct 23, 2013Group: Other
Revision 1.5Mar 29, 2017Group: Structure summary
Revision 1.6Dec 13, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_initial_refinement_model / pdbx_struct_conn_angle / struct_conn / struct_conn_type / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _pdbx_struct_conn_angle.ptnr1_PDB_ins_code / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr1_symmetry / _pdbx_struct_conn_angle.ptnr2_auth_comp_id / _pdbx_struct_conn_angle.ptnr2_auth_seq_id / _pdbx_struct_conn_angle.ptnr2_label_asym_id / _pdbx_struct_conn_angle.ptnr2_label_atom_id / _pdbx_struct_conn_angle.ptnr2_label_comp_id / _pdbx_struct_conn_angle.ptnr3_PDB_ins_code / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.ptnr3_symmetry / _pdbx_struct_conn_angle.value / _struct_conn.conn_type_id / _struct_conn.id / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.pdbx_ptnr1_PDB_ins_code / _struct_conn.pdbx_ptnr2_PDB_ins_code / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr1_symmetry / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _struct_conn.ptnr2_symmetry / _struct_conn_type.id / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Remark 700 SHEET DETERMINATION METHOD: DSSP THE SHEETS PRESENTED AS "HB" IN EACH CHAIN ON SHEET RECORDS BELOW ... SHEET DETERMINATION METHOD: DSSP THE SHEETS PRESENTED AS "HB" IN EACH CHAIN ON SHEET RECORDS BELOW IS ACTUALLY A 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
H: THROMBIN HEAVY CHAIN
I: HIRUDIN IIIA
L: THROMBIN LIGHT CHAIN
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,8086
Polymers34,2943
Non-polymers5143
Water7,152397
1


  • Idetical with deposited unit
  • defined by software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3570 Å2
ΔGint-21.6 kcal/mol
Surface area15390 Å2
MethodPQS
Unit cell
Length a, b, c (Å)71.070, 71.510, 72.400
Angle α, β, γ (deg.)90.00, 100.25, 90.00
Int Tables number5
Space group name H-MC121
Components on special symmetry positions
IDModelComponents
11H-2050-

HOH

21H-2120-

HOH

-
Components

-
Protein , 1 types, 1 molecules H

#1: Protein THROMBIN HEAVY CHAIN /


Mass: 29594.055 Da / Num. of mol.: 1 / Fragment: CATALYTIC, RESIDUES 364-620
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Cell line (production host): OVARY / Production host: CRICETULUS GRISEUS (Chinese hamster) / References: UniProt: P00734, thrombin

-
Protein/peptide , 2 types, 2 molecules IL

#2: Protein/peptide HIRUDIN IIIA


Type: Oligopeptide / Class: Anticoagulant, Antithrombotic / Mass: 1396.450 Da / Num. of mol.: 1 / Fragment: C-TERMINUS, RESIDUES 55-65 / Source method: obtained synthetically / Source: (synth.) HIRUDO MEDICINALIS (medicinal leech)
References: UniProt: P28508, N-terminal Asp des-amino Hirudin-3A
#3: Protein/peptide THROMBIN LIGHT CHAIN /


Mass: 3303.715 Da / Num. of mol.: 1 / Fragment: LIGHT CHAIN, RESIDUES 334-361
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Cell line (production host): OVARY / Production host: CRICETULUS GRISEUS (Chinese hamster) / References: UniProt: P00734, thrombin

-
Non-polymers , 4 types, 400 molecules

#4: Chemical ChemComp-ESH / 4- [(1R,3AS,4R,8AS,8BR)- 2- (4-CHLOROBENZYL)- 1- ISOPROPYL- 3- OXODECAHYDROPYRROLO[3,4- A]PYRROLIZIN- 4- YL]BENZENECARBOXIMIDAMIDE


Mass: 451.004 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C26H31ClN4O
#5: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Na
#6: Chemical ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Ca
#7: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 397 / 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: 2.76 Å3/Da / Density % sol: 43 %
Crystal growpH: 7.4 / Details: PH 7.40

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 0.97001
DetectorType: MARRESEARCH / Detector: CCD / Date: Oct 28, 2005
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97001 Å / Relative weight: 1
ReflectionResolution: 1.3→20 Å / Num. obs: 85919 / % possible obs: 98.2 % / Observed criterion σ(I): -3 / Redundancy: 3.58 % / Rmerge(I) obs: 0.04 / Net I/σ(I): 17.8
Reflection shellResolution: 1.3→1.37 Å / Redundancy: 3.08 % / Rmerge(I) obs: 0.3 / Mean I/σ(I) obs: 4.2 / % possible all: 95.9

-
Processing

Software
NameVersionClassification
REFMAC5.2.0005refinement
XDSdata reduction
XDSdata scaling
RefinementMethod to determine structure: FOURIER SYNTHESIS
Starting model: PDB ENTRY 1OYT
Resolution: 1.3→71.25 Å / Cor.coef. Fo:Fc: 0.964 / Cor.coef. Fo:Fc free: 0.957 / SU B: 1.577 / SU ML: 0.034 / TLS residual ADP flag: LIKELY RESIDUAL / Cross valid method: THROUGHOUT / ESU R: 0.048 / ESU R Free: 0.049 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS. THE SIDE CHAIN OF ARG 75 HAS ALTERNATIVE CONFORMATIONS, ONE OF WHICH IS ON A DIAD AXIS. IT HAS NOT BEEN MODELLED.
RfactorNum. reflection% reflectionSelection details
Rfree0.199 4308 5 %RANDOM
Rwork0.18 ---
obs0.181 81614 98.2 %-
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: 24.05 Å2
Baniso -1Baniso -2Baniso -3
1--0.01 Å20 Å2-0.71 Å2
2---0.13 Å20 Å2
3----0.12 Å2
Refinement stepCycle: LAST / Resolution: 1.3→71.25 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2301 0 34 397 2732
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0120.0222462
X-RAY DIFFRACTIONr_bond_other_d0.0010.022229
X-RAY DIFFRACTIONr_angle_refined_deg1.6031.9853339
X-RAY DIFFRACTIONr_angle_other_deg0.83235197
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.0665294
X-RAY DIFFRACTIONr_dihedral_angle_2_deg33.05423.363113
X-RAY DIFFRACTIONr_dihedral_angle_3_deg11.16615435
X-RAY DIFFRACTIONr_dihedral_angle_4_deg13.2041520
X-RAY DIFFRACTIONr_chiral_restr0.1150.2350
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.022714
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02518
X-RAY DIFFRACTIONr_nbd_refined0.1960.2425
X-RAY DIFFRACTIONr_nbd_other0.1870.22324
X-RAY DIFFRACTIONr_nbtor_refined0.1790.21191
X-RAY DIFFRACTIONr_nbtor_other0.0820.21430
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1420.2283
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.0410.22
X-RAY DIFFRACTIONr_symmetry_vdw_other0.320.228
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.1410.223
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it0.7971.51455
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it1.33222355
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it1.95731056
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it2.7014.5984
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: 1.3→1.33 Å / Total num. of bins used: 20 /
RfactorNum. reflection
Rfree0.299 288
Rwork0.261 5678
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL112)L122)L132)L222)L232)L332)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T112)T122)T132)T222)T232)T332)Origin x (Å)Origin y (Å)Origin z (Å)
11.5253-0.69190.471.9467-0.70052.5848-0.0092-0.0835-0.04630.07010.02080.139-0.1132-0.2198-0.0117-0.14290.04070.0192-0.1313-0.0134-0.0836-0.10210.69824.503
21.498-0.80220.19921.4295-0.27330.98820.08650.1038-0.0805-0.0783-0.07130.04210.06010.0555-0.0152-0.14140.0195-0.0033-0.1417-0.016-0.110714.167-0.88619.895
312.6295.089-5.796211.67877.630912.97720.26010.436-0.0696-0.7144-0.1741-0.52230.1473-0.0795-0.08590.0550.0913-0.03550.1102-0.0750.03458.15-4.78-1.552
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1L1 - 14
2X-RAY DIFFRACTION2H16 - 245
3X-RAY DIFFRACTION3I1 - 6

+
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