[English] 日本語
Yorodumi
- PDB-3ldx: Discovery and Clinical Evaluation of RWJ-671818, a Thrombin Inhib... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3ldx
TitleDiscovery and Clinical Evaluation of RWJ-671818, a Thrombin Inhibitor with an Oxyguanidine P1 Motif
Components
  • Hirudin variant-1
  • Thrombin heavy chain
  • Thrombin light chain
KeywordsHYDROLASE/HYDROLASE INHIBITOR / BLOOD CLOTTING / HYDROLASE-HYDROLASE INHIBITOR COMPLEX / BLOOD COAGULATION / SERINE PROTEASE
Function / homology
Function and homology information


negative regulation of serine-type peptidase activity / 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 ...negative regulation of serine-type peptidase activity / 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 / serine-type endopeptidase inhibitor 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
Thrombin inhibitor hirudin / Hirudin / Proteinase inhibitor I14, hirudin / Hirudin/antistatin / Prothrombin/thrombin / Thrombin light chain / Thrombin light chain domain superfamily / Thrombin light chain / Kringle domain / Kringle ...Thrombin inhibitor hirudin / Hirudin / Proteinase inhibitor I14, 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 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
Chem-NLI / Prothrombin / Hirudin variant-1
Similarity search - Component
Biological speciesHomo sapiens (human)
Hirudo medicinalis (medicinal leech)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.246 Å
AuthorsSpurlino, J.C.
CitationJournal: To be Published
Title: Discovery and Clinical Evaluation of RWJ-671818, a Thrombin Inhibitor with an Oxyguanidine P1 Motif
Authors: Spurlino, J.C.
History
DepositionJan 13, 2010Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 10, 2011Provider: repository / Type: Initial release
Revision 1.1Jul 19, 2017Group: Advisory / Structure summary
Category: pdbx_molecule_features / pdbx_unobs_or_zero_occ_atoms

-
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)35,7124
Polymers35,2883
Non-polymers4231
Water82946
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3240 Å2
ΔGint-15 kcal/mol
Surface area12710 Å2
MethodPISA
Unit cell
Length a, b, c (Å)71.099, 72.008, 73.412
Angle α, β, γ (deg.)90.00, 101.06, 90.00
Int Tables number5
Space group name H-MC121

-
Components

#1: Protein/peptide Thrombin light chain / / Coagulation factor II


Mass: 4096.534 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: F2 / References: UniProt: P00734, thrombin
#2: Protein Thrombin heavy chain / / Coagulation factor II


Mass: 29780.219 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: F2 / References: UniProt: P00734, thrombin
#3: Protein/peptide Hirudin variant-1 / Hirudin-1 / Hirudin-I / Lepirudin


Mass: 1411.465 Da / Num. of mol.: 1 / Fragment: residues 55-65 / Source method: obtained synthetically / Source: (synth.) Hirudo medicinalis (medicinal leech) / References: UniProt: P01050
#4: Chemical ChemComp-NLI / N-[2-(carbamimidamidooxy)ethyl]-2-{3-[(2,2-difluoro-2-phenylethyl)amino]-6-methyl-2-oxopyrazin-1(2H)-yl}acetamide / RWJ-671818


Mass: 423.417 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C18H23F2N7O3
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 46 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION

-
Sample preparation

CrystalDensity Matthews: 2.61 Å3/Da / Density % sol: 52.93 %

-
Data collection

Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU RU200
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthRelative weight: 1
ReflectionLowest resolution: 50 Å / Num. obs: 16380

-
Processing

SoftwareName: PHENIX / Version: (phenix.refine: dev_243) / Classification: refinement
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.246→22.923 Å / SU ML: 0.29 / σ(F): 0.05 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2244 1537 9.94 %
Rwork0.1748 --
obs0.1797 15468 88.68 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 27.979 Å2 / ksol: 0.357 e/Å3
Refinement stepCycle: LAST / Resolution: 2.246→22.923 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2326 0 30 46 2402
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.012420
X-RAY DIFFRACTIONf_angle_d1.33262
X-RAY DIFFRACTIONf_dihedral_angle_d20.275932
X-RAY DIFFRACTIONf_chiral_restr0.088333
X-RAY DIFFRACTIONf_plane_restr0.011422
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.2456-2.3180.33671250.23851116X-RAY DIFFRACTION79
2.318-2.40080.29191320.21711201X-RAY DIFFRACTION85
2.4008-2.49680.24161310.21451224X-RAY DIFFRACTION86
2.4968-2.61030.2851380.21391249X-RAY DIFFRACTION88
2.6103-2.74770.27981340.20541259X-RAY DIFFRACTION89
2.7477-2.91950.24071410.1961286X-RAY DIFFRACTION90
2.9195-3.14440.26141460.19441299X-RAY DIFFRACTION91
3.1444-3.45980.21341460.15361316X-RAY DIFFRACTION92
3.4598-3.95830.16711500.13331331X-RAY DIFFRACTION93
3.9583-4.97860.15551470.11661339X-RAY DIFFRACTION93
4.9786-22.92450.19061470.16151311X-RAY DIFFRACTION89

+
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