[English] 日本語
Yorodumi
- PDB-3utu: High affinity inhibitor of human thrombin -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3utu
TitleHigh affinity inhibitor of human thrombin
Components
  • Hirudin variant-1
  • Thrombin heavy chain
  • Thrombin light chain
KeywordsHYDROLASE/HYDROLASE INHIBITOR / Serine Protease / BLOOD CLOTTING / Fibrinopeptide A / HYDROLASE-HYDROLASE INHIBITOR complex
Function / homology
Function and homology information


negative regulation of serine-type peptidase activity / positive regulation of lipid kinase activity / 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 / regulation of blood coagulation / neutrophil-mediated killing of gram-negative bacterium / ligand-gated ion channel signaling pathway ...negative regulation of serine-type peptidase activity / positive regulation of lipid kinase activity / 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 / regulation of blood coagulation / neutrophil-mediated killing of gram-negative bacterium / ligand-gated ion channel signaling pathway / Defective F8 cleavage by thrombin / Platelet Aggregation (Plug Formation) / negative regulation of astrocyte differentiation / negative regulation of platelet activation / 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 / fibrinolysis / regulation of cytosolic calcium ion concentration / 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 / negative regulation of proteolysis / Cell surface interactions at the vascular wall / lipopolysaccharide binding / positive regulation of receptor signaling pathway via JAK-STAT / 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 / blood coagulation / antimicrobial humoral immune response mediated by antimicrobial peptide / Thrombin signalling through proteinase activated receptors (PARs) / heparin binding / regulation of cell shape / positive regulation of cell growth / G alpha (q) signalling events / collagen-containing extracellular matrix / blood microparticle / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / cell surface receptor signaling pathway / positive regulation of protein phosphorylation / G protein-coupled receptor signaling pathway / endoplasmic reticulum lumen / serine-type endopeptidase activity / signaling receptor binding / calcium ion binding / positive regulation of cell population proliferation / 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 / Peptidase S1A, chymotrypsin family / Serine proteases, trypsin family, histidine active site. / 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-1TS / Prothrombin / Hirudin variant-1
Similarity search - Component
Biological speciesHomo sapiens (human)
Hirudo medicinalis (medicinal leech)
MethodX-RAY DIFFRACTION / SYNCHROTRON / AB INITIO PHASING / Resolution: 1.55 Å
AuthorsBaum, B. / Steinmetzer, T. / Heine, A. / Klebe, G.
CitationJournal: Chemmedchem / Year: 2012
Title: Beyond heparinization: design of highly potent thrombin inhibitors suitable for surface coupling
Authors: Steinmetzer, T. / Baum, B. / Biela, A. / Klebe, G. / Nowak, G. / Bucha, E.
History
DepositionNov 26, 2011Deposition site: RCSB / Processing site: PDBJ
Revision 1.0Aug 29, 2012Provider: repository / Type: Initial release
Revision 1.1Dec 12, 2012Group: Other
Revision 1.2Mar 13, 2013Group: Other
Revision 1.3Mar 12, 2014Group: Database references
Revision 1.4Nov 8, 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 1.5Dec 6, 2023Group: Data collection / Category: chem_comp_atom / chem_comp_bond / Item: _chem_comp_atom.atom_id / _chem_comp_bond.atom_id_2
Revision 1.6Nov 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-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,0236
Polymers35,2973
Non-polymers7263
Water2,828157
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3420 Å2
ΔGint-34 kcal/mol
Surface area12210 Å2
MethodPISA
Unit cell
Length a, b, c (Å)70.77, 71.35, 72.39
Angle α, β, γ (deg.)90.00, 100.65, 90.00
Int Tables number5
Space group name H-MC121
Components on special symmetry positions
IDModelComponents
11H-1066-

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-1 / Hirudin-1 / Hirudin-I / Lepirudin


Mass: 1420.451 Da / Num. of mol.: 1 / Fragment: UNP RESIDUES 54-64 / Source method: obtained synthetically / Source: (synth.) Hirudo medicinalis (medicinal leech) / References: UniProt: P01050

-
Protein , 1 types, 1 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

-
Non-polymers , 3 types, 160 molecules

#4: Chemical ChemComp-1TS / (2S)-N-[(4-carbamimidoylphenyl)methyl]-1-[(2S)-2-[(3-chloro-4-methoxybenzene)sulfonamido]-3-{[(4-cyanophenyl)methyl]carbamoyl}propanoyl]pyrrolidine-2-carboxamide


Type: peptide-like / Mass: 680.174 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C32H34ClN7O6S
#5: Chemical ChemComp-NA / SODIUM ION


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


Mass: 18.015 Da / Num. of mol.: 157 / 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: 2.54 Å3/Da / Density % sol: 51.66 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7.5
Details: PHOSPHATE BUFFER, SODIUM CHLORIDE, PEG 8000, pH 7.5, VAPOR DIFFUSION, HANGING DROP, temperature 277K

-
Data collection

DiffractionMean temperature: 110 K
Diffraction sourceSource: SYNCHROTRON / Site: BESSY / Beamline: 14.2 / Wavelength: 0.91841 Å
DetectorType: MAR CCD 165 mm / Detector: CCD / Date: May 3, 2008
RadiationMonochromator: DOUBLE CRYSTAL / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.91841 Å / Relative weight: 1
ReflectionResolution: 1.55→30 Å / Num. all: 47623 / Num. obs: 47623 / % possible obs: 92.7 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 2.5 % / Rsym value: 0.046 / Net I/σ(I): 17
Reflection shellResolution: 1.55→1.58 Å / Redundancy: 2.4 % / Mean I/σ(I) obs: 2.6 / Num. unique all: 2488 / Rsym value: 0.323 / % possible all: 96.5

-
Processing

Software
NameClassification
HKL-2000data collection
SHELXmodel building
SHELXL-97refinement
HKL-2000data reduction
HKL-2000data scaling
SHELXphasing
RefinementMethod to determine structure: AB INITIO PHASING
Starting model: PDB ENTRY 1H8D

1h8d


Resolution: 1.55→10 Å / Num. parameters: 10053 / Num. restraintsaints: 9704 / Cross valid method: FREE R / σ(F): 0 / Stereochemistry target values: Engh & Huber
Details: ANISOTROPIC SCALING APPLIED BY THE METHOD OF PARKIN, MOEZZI & HOPE, J.APPL.CRYST.28(1995)53-56
RfactorNum. reflection% reflectionSelection details
Rfree0.271 2275 5.3 %RANDOM
Rwork0.217 ---
obs0.2436 47623 84.3 %-
all-43173 --
Refine analyzeNum. disordered residues: 4 / Occupancy sum hydrogen: 0 / Occupancy sum non hydrogen: 2493
Refinement stepCycle: LAST / Resolution: 1.55→10 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2282 0 49 157 2488
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONs_bond_d0.009
X-RAY DIFFRACTIONs_angle_d0.027
X-RAY DIFFRACTIONs_similar_dist0
X-RAY DIFFRACTIONs_from_restr_planes0.0265
X-RAY DIFFRACTIONs_zero_chiral_vol0.049
X-RAY DIFFRACTIONs_non_zero_chiral_vol0.06
X-RAY DIFFRACTIONs_anti_bump_dis_restr0.013
X-RAY DIFFRACTIONs_rigid_bond_adp_cmpnt0
X-RAY DIFFRACTIONs_similar_adp_cmpnt0.082
X-RAY DIFFRACTIONs_approx_iso_adps0

+
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