[English] 日本語
Yorodumi
- PDB-3uwj: Human Thrombin In Complex With MI353 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3uwj
TitleHuman Thrombin In Complex With MI353
Components
  • Hirudin variant-2
  • Thrombin Heavy Chain
  • Thrombin Light Chain
KeywordsHYDROLASE/HYDROLASE INHIBITOR / Serine Protease / Kringle / Hydrolase / Blood Coagulation / Blood Clotting / Convertion Of Fibrinogen To Fibrin / Cleavage On Pairs Of Basic Residues / Hirudin / Glycosylation / Blood / HYDROLASE-HYDROLASE INHIBITOR complex
Function / homology
Function and homology information


cytolysis by host of symbiont cells / thrombospondin receptor activity / Defective factor XII causes hereditary angioedema / thrombin / thrombin-activated receptor signaling pathway / 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 / Defective factor XII causes hereditary angioedema / thrombin / thrombin-activated receptor signaling pathway / 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 / 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 / Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus / regulation of cytosolic calcium ion concentration / 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 / Peptide ligand-binding receptors / Regulation of Complement cascade / positive regulation of release of sequestered calcium ion into cytosol / acute-phase response / Cell surface interactions at the vascular wall / positive regulation of receptor signaling pathway via JAK-STAT / growth factor activity / lipopolysaccharide binding / 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 / blood coagulation / antimicrobial humoral immune response mediated by antimicrobial peptide / 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
N-(BENZYLSULFONYL)-D-LEUCYL-N-(4-CARBAMIMIDOYLBENZYL)-L-PROLINAMIDE / PHOSPHATE ION / Chem-TIF / Prothrombin / Hirudin variant-2
Similarity search - Component
Biological speciesHomo sapiens (human)
Hirudo medicinalis (medicinal leech)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.5 Å
AuthorsBiela, A. / Heine, A. / Klebe, G.
CitationJournal: J.Med.Chem. / Year: 2012
Title: Ligand binding stepwise disrupts water network in thrombin: enthalpic and entropic changes reveal classical hydrophobic effect
Authors: Biela, A. / Sielaff, F. / Terwesten, F. / Heine, A. / Steinmetzer, T. / Klebe, G.
History
DepositionDec 2, 2011Deposition site: RCSB / Processing site: PDBJ
Revision 1.0Dec 12, 2012Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2016Group: Database references
Revision 1.2Jul 29, 2020Group: Data collection / Derived calculations / Structure summary
Category: chem_comp / entity ...chem_comp / entity / pdbx_chem_comp_identifier / pdbx_entity_nonpoly / struct_conn / struct_site / struct_site_gen
Item: _chem_comp.name / _chem_comp.type ..._chem_comp.name / _chem_comp.type / _entity.pdbx_description / _pdbx_entity_nonpoly.name / _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.pdbx_role / _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.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
Description: Carbohydrate remediation / Provider: repository / Type: Remediation
Revision 1.3Nov 8, 2023Group: Data collection / Database references ...Data collection / Database references / Refinement description / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _chem_comp.pdbx_synonyms / _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.4Dec 6, 2023Group: Data collection / Category: chem_comp_atom / chem_comp_bond / Item: _chem_comp_atom.atom_id / _chem_comp_bond.atom_id_2
Revision 1.5Nov 20, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
L: Thrombin Light Chain
H: Thrombin Heavy Chain
I: Hirudin variant-2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,9299
Polymers35,5393
Non-polymers1,3896
Water6,287349
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4010 Å2
ΔGint-35 kcal/mol
Surface area12850 Å2
MethodPISA
Unit cell
Length a, b, c (Å)70.300, 71.200, 72.400
Angle α, β, γ (deg.)90.00, 100.70, 90.00
Int Tables number5
Space group name H-MC121
Components on special symmetry positions
IDModelComponents
11H-1062-

HOH

21H-1267-

HOH

-
Components

-
Protein/peptide , 2 types, 2 molecules LI

#1: Protein/peptide Thrombin Light Chain


Mass: 4096.534 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P00734, thrombin
#3: Protein/peptide Hirudin variant-2


Mass: 1662.683 Da / Num. of mol.: 1 / Fragment: residues in UNP 60-72 / Source method: obtained synthetically / Details: Synthetic Fragment of Hirudo Medicinalis / Source: (synth.) Hirudo medicinalis (medicinal leech) / References: UniProt: P09945

-
Protein / Sugars , 2 types, 2 molecules H

#2: Protein Thrombin Heavy Chain


Mass: 29780.219 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P00734, thrombin
#4: Sugar ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0

-
Non-polymers , 4 types, 354 molecules

#5: Chemical ChemComp-TIF / N-(benzylsulfonyl)-D-leucyl-N-(4-carbamimidoylbenzyl)-L-prolinamide


Type: peptide-like, Peptide-like / Class: Thrombin inhibitor / Mass: 513.652 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C26H35N5O4S
References: N-(BENZYLSULFONYL)-D-LEUCYL-N-(4-CARBAMIMIDOYLBENZYL)-L-PROLINAMIDE
#6: Chemical ChemComp-PO4 / PHOSPHATE ION


Mass: 94.971 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: PO4
#7: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Na
#8: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 349 / Source method: isolated from a natural source / Formula: H2O

-
Details

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: 50.9 %
Crystal growTemperature: 277.15 K / Method: vapor diffusion, hanging drop / pH: 7.5
Details: 15% PEG 8000, 20mM sodium phosphate, 175mM sodium chloride, pH 7.5, VAPOR DIFFUSION, HANGING DROP, temperature 277.15K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: BESSY / Beamline: 14.2 / Wavelength: 0.91841 Å
DetectorType: RAYONIX MX-225 / Detector: CCD / Date: Jun 25, 2010 / Details: Collimating Mirror
RadiationMonochromator: Double Crystal Monochromator / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.91841 Å / Relative weight: 1
ReflectionResolution: 1.5→50 Å / Num. all: 55148 / Num. obs: 55148 / % possible obs: 97.3 % / Redundancy: 2.7 % / Biso Wilson estimate: 13.66 Å2 / Rsym value: 0.053 / Net I/σ(I): 17.7
Reflection shellResolution: 1.5→1.53 Å / Redundancy: 2.6 % / Mean I/σ(I) obs: 1.9 / Num. unique all: 2816 / Rsym value: 0.468 / % possible all: 98.5

-
Processing

Software
NameVersionClassification
MAR345dtbdata collection
PHASERphasing
PHENIX(phenix.refine: 1.7_650)refinement
HKL-2000data reduction
HKL-2000data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1H8D

1h8d


Resolution: 1.5→22.496 Å / Occupancy max: 1 / Occupancy min: 0.19 / FOM work R set: 0.8976 / SU ML: 0.19 / Cross valid method: Free R / σ(F): 0 / Phase error: 17.5 / Stereochemistry target values: ML
RfactorNum. reflection% reflectionSelection details
Rfree0.1828 2635 5.07 %Random
Rwork0.1601 ---
all0.1613 54651 --
obs0.1613 52016 92.72 %-
Solvent computationShrinkage radii: 0.72 Å / VDW probe radii: 1 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 59.119 Å2 / ksol: 0.4 e/Å3
Displacement parametersBiso max: 100.19 Å2 / Biso mean: 22.1079 Å2 / Biso min: 6.52 Å2
Baniso -1Baniso -2Baniso -3
1-1.3047 Å20 Å2-3.2169 Å2
2---1.9783 Å2-0 Å2
3---0.6735 Å2
Refinement stepCycle: LAST / Resolution: 1.5→22.496 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2341 0 68 349 2758
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0182574
X-RAY DIFFRACTIONf_angle_d1.0953499
X-RAY DIFFRACTIONf_dihedral_angle_d16.8851019
X-RAY DIFFRACTIONf_chiral_restr0.074366
X-RAY DIFFRACTIONf_plane_restr0.005443
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 19

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
1.5-1.52730.27781140.2629235584
1.5273-1.55660.25481280.2286242987
1.5566-1.58840.21031150.2095247489
1.5884-1.62290.2131710.1987251191
1.6229-1.66070.1851200.1839254891
1.6607-1.70220.21281550.1789250891
1.7022-1.74820.19841330.1734259492
1.7482-1.79960.2281480.1601262594
1.7996-1.85770.19561350.1569266294
1.8577-1.9240.19841300.1594262494
1.924-2.0010.17791430.1535264795
2.001-2.0920.18671320.152268596
2.092-2.20220.16551340.1486268896
2.2022-2.34010.18171450.1587267495
2.3401-2.52060.17711480.1542270496
2.5206-2.77380.19461550.1691267195
2.7738-3.17420.19351570.1614267295
3.1742-3.99550.1641230.1393267294
3.9955-22.49840.14881490.1491263892
Refinement TLS params.

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

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
10.3559-0.2204-0.19650.45010.16780.42520.26220.2747-0.2804-0.1951-0.13460.12050.194-0.01160.19960.15830.0852-0.04230.166-0.0690.12198.1912-2.739311.3984
20.2519-0.23750.21620.4817-0.19190.26430.25040.43130.0088-0.275-0.2554-0.12020.12070.1977-0.08250.16220.1206-0.00050.2244-0.02590.087816.2362-1.08978.7928
30.39780.40790.00980.54370.26860.69680.21540.22720.00820.0086-0.0405-0.1990.05890.23680.33420.08210.06360.0280.19280.02810.116125.7574-0.961816.6078
40.4249-0.3484-0.06930.28810.02050.09290.03180.04450.03780.0002-0.0264-0.0328-0.03370.0146-0.0030.10990.0306-0.00920.0914-0.01140.08099.36895.972123.3798
50.587-0.36330.25370.2362-0.18850.36780.03040.0098-0.2680.0458-0.01150.26370.1602-0.0157-0.08430.12410.0133-0.02390.06390.00450.11267.9295-9.545826.887
60.4902-0.11990.15730.1565-0.0530.33770.0401-0.0568-0.140.03660.00640.05820.0809-0.00780.0030.10340.01680.00140.08180.00260.108510.6306-4.08628.0656
70.82860.6844-1.38891.0063-1.18252.41110.0796-0.04020.25170.043-0.012-0.1727-0.28960.1844-0.03680.1467-0.02410.01930.15650.00660.253326.87788.878821.978
80.0037-0.0231-0.01090.17470.08230.03970.07740.10080.007-0.15020.0265-0.0512-0.10730.03360.09360.40920.19110.0410.5288-0.1130.101412.0755-1.5468-3.5295
90.3329-0.40650.15260.9271-0.22050.40360.0110.05970.1129-0.1042-0.125-0.1093-0.2332-0.05120.02950.15390.05620.00510.12160.00240.11512.87515.31518.2363
101.0303-0.005500.0703-0.01560.06080.0187-0.0357-0.1069-0.0417-0.0680.0349-0.0168-0.13450.02960.10810.04260.00340.1737-0.00730.119-4.8887.533422.7639
110.08220.11470.08520.22790.02240.36010.0596-0.0694-0.00140.00610.09180.0027-0.0578-0.1824-0.05350.13250.03620.05260.16370.00150.1459-1.27975.157333.1978
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1(chain H and resid 16:41)H16 - 41
2X-RAY DIFFRACTION2(chain H and resid 42:83)H42 - 83
3X-RAY DIFFRACTION3(chain H and resid 84:111)H84 - 111
4X-RAY DIFFRACTION4(chain H and resid 112:144)H112 - 144
5X-RAY DIFFRACTION5(chain H and resid 145:173)H145 - 173
6X-RAY DIFFRACTION6(chain H and resid 174:232)H174 - 232
7X-RAY DIFFRACTION7(chain H and resid 233:246)H233 - 246
8X-RAY DIFFRACTION8(chain I and resid 55:65)I55 - 65
9X-RAY DIFFRACTION9(chain L and resid 1C:11)L1
10X-RAY DIFFRACTION10(chain L and resid 12:14C)L12 - 14
11X-RAY DIFFRACTION11(chain L and resid 14D:14K)L14

+
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