[English] 日本語
Yorodumi
- PDB-6z48: Crystal structure of Thrombin in complex with macrocycle X1vE -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6z48
TitleCrystal structure of Thrombin in complex with macrocycle X1vE
Components
  • Thrombin heavy chain
  • Thrombin light chain
KeywordsHYDROLASE / serine protease / blood clotting factor / inhibition / macrocycle
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 / 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 / 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 / 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
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
Chem-X1V / Prothrombin
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.27 Å
AuthorsAngelini, A. / Habeshian, S. / Heinis, C. / Cendron, L.
Funding support Switzerland, 1items
OrganizationGrant numberCountry
Swiss National Science Foundation157842 Switzerland
CitationJournal: Nat Commun / Year: 2022
Title: Synthesis and direct assay of large macrocycle diversities by combinatorial late-stage modification at picomole scale.
Authors: Habeshian, S. / Merz, M.L. / Sangouard, G. / Mothukuri, G.K. / Schuttel, M. / Bognar, Z. / Diaz-Perlas, C. / Vesin, J. / Bortoli Chapalay, J. / Turcatti, G. / Cendron, L. / Angelini, A. / Heinis, C.
History
DepositionMay 23, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jun 1, 2022Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2022Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Jan 24, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Revision 1.3Nov 13, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
L: Thrombin light chain
H: Thrombin heavy chain
A: Thrombin light chain
B: Thrombin heavy chain
C: Thrombin light chain
D: Thrombin heavy chain
E: Thrombin light chain
F: Thrombin heavy chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)138,10416
Polymers135,5078
Non-polymers2,5978
Water7,188399
1
L: Thrombin light chain
H: Thrombin heavy chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,5264
Polymers33,8772
Non-polymers6492
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2320 Å2
ΔGint-22 kcal/mol
Surface area12770 Å2
MethodPISA
2
A: Thrombin light chain
B: Thrombin heavy chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,5264
Polymers33,8772
Non-polymers6492
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2280 Å2
ΔGint-21 kcal/mol
Surface area12570 Å2
MethodPISA
3
C: Thrombin light chain
D: Thrombin heavy chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,5264
Polymers33,8772
Non-polymers6492
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2230 Å2
ΔGint-22 kcal/mol
Surface area12940 Å2
MethodPISA
4
E: Thrombin light chain
F: Thrombin heavy chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,5264
Polymers33,8772
Non-polymers6492
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2320 Å2
ΔGint-20 kcal/mol
Surface area12530 Å2
MethodPISA
Unit cell
Length a, b, c (Å)56.251, 100.573, 108.897
Angle α, β, γ (deg.)90.000, 90.110, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein/peptide
Thrombin light chain


Mass: 4096.534 Da / Num. of mol.: 4 / Source method: isolated from a natural source
Details: >sp|P00734|328-363; missing residues are not visible in the electron density maps / disordered regions;
Source: (natural) Homo sapiens (human) / References: UniProt: P00734
#2: Protein
Thrombin heavy chain


Mass: 29780.219 Da / Num. of mol.: 4 / Source method: isolated from a natural source
Details: >sp|P00734|364-622; missing residues are not visible in the electron density maps / disordered regions
Source: (natural) Homo sapiens (human) / References: UniProt: P00734
#3: Chemical
ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Na
#4: Chemical
ChemComp-X1V / 5-chloranyl-N-[[(4S,15R)-2,5,13,16-tetrakis(oxidanylidene)-15-propan-2-yl-9,10-dithia-3,6,14,17-tetrazabicyclo[17.3.1]tricosa-1(22),19(23),20-trien-4-yl]methyl]thiophene-2-carboxamide / macrocycle X1vE / 5-chloro-N-[[(4S,15R)-15-isopropyl-2,5,13,16-tetraoxo-9,10-dithia-3,6,14,17-tetrazabicyclo[17.3.1]tricosa-1(22),19(23),20-trien-4-yl]methyl]thiophene-2-carboxamide


Type: peptide-like / Mass: 626.211 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Formula: C26H32ClN5O5S3 / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 399 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.38 Å3/Da / Density % sol: 48.22 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 7.5
Details: 100 mM MOPS/sodium HEPES pH 7.5, 12.5% w/v PEG 1000, 12.5% w/v PEG 3350, 12.5% v/v MPD

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.97949 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Oct 8, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97949 Å / Relative weight: 1
ReflectionResolution: 2.27→108.02 Å / Num. obs: 52645 / % possible obs: 93.86 % / Redundancy: 2 % / CC1/2: 0.998 / Rmerge(I) obs: 0.041 / Net I/σ(I): 16.7
Reflection shellResolution: 2.27→2.35 Å / Rmerge(I) obs: 0.2527 / Num. unique obs: 4712 / CC1/2: 0.794

-
Processing

Software
NameVersionClassification
REFMAC5.8.0258refinement
PDB_EXTRACT3.25data extraction
Aimlessdata reduction
SCALAdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6GWE

6gwe


Resolution: 2.27→73.88 Å / Cross valid method: THROUGHOUT
RfactorNum. reflection% reflectionSelection details
Rfree0.2425 --RANDOM
Rwork0.1887 ---
obs-52631 93.86 %-
Displacement parametersBiso max: 135.43 Å2 / Biso mean: 28.0801 Å2 / Biso min: 5.48 Å2
Refinement stepCycle: LAST / Resolution: 2.27→73.88 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms9098 0 164 399 9661

+
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