[English] 日本語
Yorodumi
- PDB-3b23: Crystal structure of thrombin-variegin complex: Insights of a nov... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3b23
TitleCrystal structure of thrombin-variegin complex: Insights of a novel mechanism of inhibition and design of tunable thrombin inhibitors
Components
  • Thrombin heavy chain
  • Thrombin light chain
  • Variegin
KeywordsHYDROLASE/HYDROLASE INHIBITOR / HYDROLASE-HYDROLASE INHIBITOR complex
Function / homology
Function and homology information


molecular function inhibitor 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-activated receptor signaling pathway / thrombin / neutrophil-mediated killing of gram-negative bacterium / regulation of blood coagulation / Defective F8 cleavage by thrombin ...molecular function inhibitor 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-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 / serine-type endopeptidase inhibitor 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
Prothrombin / Variegin
Similarity search - Component
Biological speciesHomo sapiens (human)
Amblyomma variegatum (tropical bont tick)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.4 Å
AuthorsKoh, C.Y. / Kumar, S. / Swaminathan, K. / Kini, R.M.
CitationJournal: Plos One / Year: 2011
Title: Crystal structure of thrombin in complex with s-variegin: insights of a novel mechanism of inhibition and design of tunable thrombin inhibitors
Authors: Koh, C.Y. / Kumar, S. / Kazimirova, M. / Nuttall, P.A. / Radhakrishnan, U.P. / Kim, S. / Jagadeeswaran, P. / Imamura, T. / Mizuguchi, J. / Iwanaga, S. / Swaminathan, K. / Kini, R.M.
History
DepositionJul 20, 2011Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Nov 23, 2011Provider: repository / Type: Initial release
Revision 1.1Nov 1, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.2Nov 6, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Thrombin light chain
B: Thrombin heavy chain
C: Variegin


Theoretical massNumber of molelcules
Total (without water)37,4893
Polymers37,4893
Non-polymers00
Water91951
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3960 Å2
ΔGint-10 kcal/mol
Surface area14300 Å2
MethodPISA
Unit cell
Length a, b, c (Å)124.658, 50.826, 61.535
Angle α, β, γ (deg.)90.00, 98.70, 90.00
Int Tables number5
Space group name H-MC121

-
Components

#1: Protein/peptide Thrombin light chain / alpha-thrombin / light chain


Mass: 4096.534 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: F2 / Plasmid: pCAGG/mdhfr/prethrombin-2
Cell line (production host): SP2/0 Ag14 mouse myeloma cells (ATCC CRL-1581)
Production host: Mus musculus (house mouse) / References: UniProt: P00734, thrombin
#2: Protein Thrombin heavy chain / alpha-thrombin / heavy chain


Mass: 29780.219 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: F2 / Plasmid: pCAGG/mdhfr/prethrombin-2
Cell line (production host): SP2/0 Ag14 mouse myeloma cells (ATCC CRL-1581)
Production host: Mus musculus (house mouse) / References: UniProt: P00734, thrombin
#3: Protein/peptide Variegin


Mass: 3611.825 Da / Num. of mol.: 1 / Source method: obtained synthetically
Details: Peptide is chemically synthesized based on sequence of a thrombin inhibitor found in the salivary gland extract of Amblyomma variegatum
Source: (synth.) Amblyomma variegatum (tropical bont tick) / References: UniProt: P85800
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 51 / 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: 2.57 Å3/Da / Density % sol: 52.14 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7.4
Details: 100mM HEPES buffer pH 7.4, 20-25% (w/v) PEG 8000, VAPOR DIFFUSION, HANGING DROP, temperature 277K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: NSLS / Beamline: X29A / Wavelength: 0.9795 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Sep 28, 2007
RadiationMonochromator: Si 111 CHANNEL / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 2.4→50 Å / Num. obs: 15137 / % possible obs: 98.1 % / Observed criterion σ(I): -3 / Redundancy: 3.6 % / Rmerge(I) obs: 0.053 / Net I/σ(I): 20
Reflection shellResolution: 2.4→2.46 Å / Redundancy: 3.1 % / Rmerge(I) obs: 0.154 / Mean I/σ(I) obs: 5.4 / % possible all: 97

-
Processing

Software
NameVersionClassification
PHASERphasing
REFMAC5.5.0109refinement
HKL-2000data reduction
HKL-2000data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1ABI

1abi


Resolution: 2.4→30 Å / Cor.coef. Fo:Fc: 0.946 / Cor.coef. Fo:Fc free: 0.923 / SU B: 19.862 / SU ML: 0.208 / Isotropic thermal model: Isotropic & TLS / Cross valid method: THROUGHOUT / ESU R Free: 0.283 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.25944 724 5.2 %RANDOM
Rwork0.20787 ---
obs0.21049 13298 92.82 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso mean: 57.826 Å2
Baniso -1Baniso -2Baniso -3
1--1.05 Å20 Å2-4.79 Å2
2--2.49 Å20 Å2
3----2.88 Å2
Refinement stepCycle: LAST / Resolution: 2.4→30 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2464 0 0 51 2515
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.010.0222534
X-RAY DIFFRACTIONr_bond_other_d0.0010.021793
X-RAY DIFFRACTIONr_angle_refined_deg1.2241.9583427
X-RAY DIFFRACTIONr_angle_other_deg0.81134343
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.8185302
X-RAY DIFFRACTIONr_dihedral_angle_2_deg32.42623.471121
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.32715444
X-RAY DIFFRACTIONr_dihedral_angle_4_deg19.2291520
X-RAY DIFFRACTIONr_chiral_restr0.0730.2355
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.0212786
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02529
X-RAY DIFFRACTIONr_mcbond_it0.491.51516
X-RAY DIFFRACTIONr_mcbond_other0.0781.5613
X-RAY DIFFRACTIONr_mcangle_it0.93122447
X-RAY DIFFRACTIONr_scbond_it1.19131018
X-RAY DIFFRACTIONr_scangle_it1.9364.5980
LS refinement shellResolution: 2.4→2.462 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.388 44 -
Rwork0.276 659 -
obs--63.79 %
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)
17.7683-5.39544.30747.535-4.21337.22610.61510.1421-0.4183-0.3334-0.26570.58260.9106-0.379-0.34940.2998-0.1234-0.1240.1748-0.04980.20814.0794-16.84688.3862
23.0952-0.15131.95262.2568-0.40624.9670.15320.37640.16390.1246-0.2425-0.14380.07030.8190.08920.0587-0.029-0.0150.18840.04460.055820.3728-8.373814.5645
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A1 - 14
2X-RAY DIFFRACTION2B16 - 247

+
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