[English] 日本語
Yorodumi
- PDB-6cym: Reversible Covalent Direct Thrombin Inhibitors -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6cym
TitleReversible Covalent Direct Thrombin Inhibitors
Components(ProthrombinThrombin) x 2
KeywordsHydrolase/Hydrolase Inhibitor / Hydrolase / blood coagulation / plasma / calcium-binding / glycoprotein / serine protease / 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 / 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 / Cell surface interactions at the vascular wall / lipopolysaccharide binding / negative regulation of proteolysis / positive regulation of receptor signaling pathway via JAK-STAT / growth factor activity / positive regulation of insulin secretion / platelet activation / response to wounding / 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 / positive regulation of cell growth / G alpha (q) signalling events / collagen-containing extracellular matrix / blood microparticle / cell surface receptor signaling pathway / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of protein phosphorylation / G protein-coupled receptor signaling pathway / 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
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. ...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. / Serine proteases, trypsin family, serine active site. / 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
2-methoxybenzoic acid / Prothrombin
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 2.9 Å
AuthorsSivaraja, M. / Williams, D.C.
CitationJournal: PLoS ONE / Year: 2018
Title: Reversible covalent direct thrombin inhibitors.
Authors: Sivaraja, M. / Pozzi, N. / Rienzo, M. / Lin, K. / Shiau, T.P. / Clemens, D.M. / Igoudin, L. / Zalicki, P. / Chang, S.S. / Estiarte, M.A. / Short, K.M. / Williams, D.C. / Datta, A. / Di Cera, E. / Kita, D.B.
History
DepositionApr 6, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 9, 2018Provider: repository / Type: Initial release
Revision 1.1Aug 15, 2018Group: Data collection / 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 / _citation_author.identifier_ORCID
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 / pdbx_struct_conn_angle / 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 / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _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_role / _struct_conn.pdbx_value_order / _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
Description: Carbohydrate remediation / Provider: repository / Type: Remediation

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Prothrombin
B: Prothrombin
C: Prothrombin
D: Prothrombin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)66,7399
Polymers66,1684
Non-polymers5715
Water39622
1
A: Prothrombin
B: Prothrombin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,4805
Polymers33,0842
Non-polymers3963
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2500 Å2
ΔGint-19 kcal/mol
Surface area12640 Å2
MethodPISA
2
C: Prothrombin
D: Prothrombin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,2594
Polymers33,0842
Non-polymers1752
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2330 Å2
ΔGint-21 kcal/mol
Surface area12910 Å2
MethodPISA
Unit cell
Length a, b, c (Å)91.670, 99.730, 146.010
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number20
Space group name H-MC2221

-
Components

-
Protein / Protein/peptide / Sugars , 3 types, 5 molecules ACBD

#1: Protein Prothrombin / Thrombin / Coagulation factor II


Mass: 29780.219 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P00734, thrombin
#2: Protein/peptide Prothrombin / Thrombin / Coagulation factor II


Mass: 3303.715 Da / Num. of mol.: 2 / 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-Acetylglucosamine


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 , 3 types, 26 molecules

#3: Chemical ChemComp-71F / 2-methoxybenzoic acid / Anisic acid


Mass: 152.147 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C8H8O3
#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 / Water


Mass: 18.015 Da / Num. of mol.: 22 / 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: 2.52 Å3/Da / Density % sol: 51.22 %
Crystal growTemperature: 294 K / Method: batch mode
Details: For complex formation, 2 mg human alpha-thrombin (7.1 mg/mL in 50% v/v glycerol) were mixed with 0.5 mM Compound 1 in DMSO and dialyzed overnight into a solution of 20 mM sodium citrate and ...Details: For complex formation, 2 mg human alpha-thrombin (7.1 mg/mL in 50% v/v glycerol) were mixed with 0.5 mM Compound 1 in DMSO and dialyzed overnight into a solution of 20 mM sodium citrate and 1.3 mM Na2SO4 (pH 5.8). After dialysis, another 0.5 mM compound were added and left to incubate at room temperature for 1 h. The protein was centrifuged for 5 min at 4 deg C and 8000x RCF. The pellet, including about 120 uL of buffer, was mixed with 100 uL of a solution containing 50 mM sodium phosphate (pH 7.3), 190 mM sodium chloride, and 0.2 mM Compound 1. The crystal used for data collection was grown from the JCSG+ screen in well A10. The crystal was grown at 20 deg C using a MRC 3-well plate and in a 150 + 150 nL drop with a reservoir of 0.2 M potassium formate and 20% w/v PEG-3350.

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.97625 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Dec 15, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97625 Å / Relative weight: 1
ReflectionResolution: 2.9→30 Å / Num. obs: 10936 / % possible obs: 72.1 % / Redundancy: 6.5 % / Biso Wilson estimate: 73.56 Å2 / Net I/σ(I): 8.2
Reflection shellResolution: 2.9→2.95 Å

-
Processing

Software
NameVersionClassification
BUSTER2.11.7refinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementResolution: 2.9→30 Å / Cor.coef. Fo:Fc: 0.915 / Cor.coef. Fo:Fc free: 0.856 / Cross valid method: THROUGHOUT / σ(F): 0 / SU Rfree Blow DPI: 0.521
RfactorNum. reflection% reflectionSelection details
Rfree0.254 566 5.18 %RANDOM
Rwork0.176 ---
obs0.18 10936 72.1 %-
Displacement parametersBiso mean: 69.84 Å2
Baniso -1Baniso -2Baniso -3
1--5.9755 Å20 Å20 Å2
2--8.7076 Å20 Å2
3----2.7322 Å2
Refine analyzeLuzzati coordinate error obs: 0.35 Å
Refinement stepCycle: 1 / Resolution: 2.9→30 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4556 0 36 22 4614
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.014712HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.196361HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d1670SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes112HARMONIC2
X-RAY DIFFRACTIONt_gen_planes671HARMONIC5
X-RAY DIFFRACTIONt_it4712HARMONIC20
X-RAY DIFFRACTIONt_nbd0SEMIHARMONIC5
X-RAY DIFFRACTIONt_omega_torsion2.89
X-RAY DIFFRACTIONt_other_torsion22.45
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion579SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact5212SEMIHARMONIC4
LS refinement shellResolution: 2.9→3.18 Å / Total num. of bins used: 6
RfactorNum. reflection% reflection
Rfree0.3143 -5.21 %
Rwork0.204 1220 -
all0.21 1287 -
obs--36.04 %
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)
11.28521.26762.26180.4815-1.07765.17770.00410.01470.15490.20610.1386-0.5442-0.5320.2907-0.1427-0.1993-0.2387-0.02970.1434-0.07020.01212.205138.755114.9259
23.558-0.74930.08292.06740.42074.05020.11660.55910.1481-0.1790.011-0.1453-0.05880.1112-0.1275-0.3465-0.01740.03540.0663-0.0417-0.25422.346528.41972.2338
35.65871.29350.9651.366-1.90396.49140.0520.02520.0996-0.0383-0.0544-0.48590.06820.07060.0024-0.47820.1035-0.0730.5630.0833-0.123433.250322.893343.1849
44.0126-0.59811.85132.43020.34315.39780.4630.7828-0.6963-0.2097-0.1113-0.22261.08850.982-0.3518-0.33310.304-0.0740.1296-0.1172-0.374819.208612.1535.8613
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1{ B|1 - B|27 }
2X-RAY DIFFRACTION2{ A|15 - A|271 }
3X-RAY DIFFRACTION3{ D|1 - D|27 }
4X-RAY DIFFRACTION4{ C|15 - C|271 }

+
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