[English] 日本語
Yorodumi
- PDB-2r2m: 2-(2-Chloro-6-Fluorophenyl)Acetamides as Potent Thrombin Inhibitors -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2r2m
Title2-(2-Chloro-6-Fluorophenyl)Acetamides as Potent Thrombin Inhibitors
Components
  • Hirudin-3A
  • Thrombin heavy chain
  • Thrombin light chain
KeywordsHYDROLASE/HYDROLASE INHIBITOR / Thrombin / Acute phase / Blood coagulation / Cleavage on pair of basic residues / Disease mutation / Gamma-carboxyglutamic acid / Glycoprotein / Kringle / Protease / Secreted / Serine protease / Zymogen / Protease inhibitor / Serine protease inhibitor / Sulfation / 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 / regulation of blood coagulation / neutrophil-mediated killing of gram-negative bacterium / 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 / 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 / acute-phase response / Regulation of Complement cascade / 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 / 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 / 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 / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / cell surface receptor signaling pathway / blood microparticle / 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
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-I50 / Prothrombin / Hirudin variant-2 / Hirudin-3A
Similarity search - Component
Biological speciesHomo sapiens (human)
Hirudo medicinalis (medicinal leech)
MethodX-RAY DIFFRACTION / Resolution: 2.1 Å
AuthorsSpurlino, J.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2007
Title: 2-(2-Chloro-6-Fluorophenyl)Acetamides as Potent Thrombin Inhibitors
Authors: Lee, L. / Kreutter, K.D. / Pan, W. / Crysler, C. / Spurlino, J. / Player, M.R. / Tomczuk, B. / Lu, T.
History
DepositionAug 27, 2007Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 26, 2008Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Atomic model / Database references ...Atomic model / Database references / Derived calculations / Non-polymer description / Structure summary / Version format compliance

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Thrombin light chain
B: Thrombin heavy chain
H: Hirudin-3A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,7114
Polymers34,2673
Non-polymers4441
Water2,468137
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3260 Å2
Unit cell
Length a, b, c (Å)70.950, 72.135, 72.850
Angle α, β, γ (deg.)90.00, 100.64, 90.00
Int Tables number5
Space group name H-MC121
Components on special symmetry positions
IDModelComponents
11B-106-

ARG

-
Components

#1: Protein/peptide Thrombin light chain


Mass: 3075.470 Da / Num. of mol.: 1 / Fragment: unp residues 334-359 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P00734, thrombin
#2: Protein 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 / References: UniProt: P00734, thrombin
#3: Protein/peptide Hirudin-3A / Hirudin IIIA


Mass: 1411.465 Da / Num. of mol.: 1 / Fragment: unp residues 55-65
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Hirudo medicinalis (medicinal leech) / References: UniProt: P28507, UniProt: P09945*PLUS
#4: Chemical ChemComp-I50 / N-[2-({[amino(imino)methyl]amino}oxy)ethyl]-2-{6-chloro-3-[(2,2-difluoro-2-phenylethyl)amino]-2-fluorophenyl}acetamide


Mass: 443.851 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C19H21ClF3N5O2
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 137 / 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: 2.67 Å3/Da / Density % sol: 53.95 %

-
Data collection

Diffraction sourceSource: ROTATING ANODE / Type: ENRAF-NONIUS FR591
DetectorType: RIGAKU RAXIS II / Detector: IMAGE PLATE / Date: Mar 6, 2001
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthRelative weight: 1
ReflectionResolution: 2.1→20 Å / Num. obs: 18902 / Biso Wilson estimate: 23.65 Å2

-
Processing

Software
NameVersionClassificationNB
PHENIXrefinement
PDB_EXTRACT3data extraction
X-PLORphasing
RefinementResolution: 2.1→20 Å / Stereochemistry target values: ml
RfactorNum. reflection% reflection
Rfree0.214 1873 9.91 %
Rwork0.168 --
obs-18902 89.25 %
Solvent computationBsol: 44.364 Å2 / ksol: 0.366 e/Å3
Displacement parametersBiso mean: 29.99 Å2
Baniso -1Baniso -2Baniso -3
1-3.931 Å20 Å2-4.529 Å2
2---4.372 Å2-0 Å2
3---0.442 Å2
Refinement stepCycle: LAST / Resolution: 2.1→20 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2332 0 30 137 2499
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONf_bond_d0.004
X-RAY DIFFRACTIONf_angle_d0.599
X-RAY DIFFRACTIONf_dihedral_angle_d11.805
X-RAY DIFFRACTIONf_chiral_restr0.052
X-RAY DIFFRACTIONf_plane_restr0.002
LS refinement shell
Resolution (Å)Rfactor RworkNum. reflection RworkRefine-IDTotal num. of bins used% reflection obs (%)
2.1-2.1210.252343X-RAY DIFFRACTION3455
2.121-2.1430.235374X-RAY DIFFRACTION3462
2.143-2.1660.248377X-RAY DIFFRACTION3461
2.166-2.190.238438X-RAY DIFFRACTION3467
2.19-2.2140.216414X-RAY DIFFRACTION3468
2.214-2.240.235433X-RAY DIFFRACTION3471
2.24-2.2680.24453X-RAY DIFFRACTION3475
2.268-2.2960.219489X-RAY DIFFRACTION3475
2.296-2.3270.221458X-RAY DIFFRACTION3476
2.327-2.3590.216475X-RAY DIFFRACTION3477
2.359-2.3920.205494X-RAY DIFFRACTION3480
2.392-2.4280.194494X-RAY DIFFRACTION3478
2.428-2.4660.2477X-RAY DIFFRACTION3480
2.466-2.5060.186518X-RAY DIFFRACTION3481
2.506-2.550.199502X-RAY DIFFRACTION3481
2.55-2.5960.203534X-RAY DIFFRACTION3486
2.596-2.6460.199535X-RAY DIFFRACTION3487
2.646-2.70.197536X-RAY DIFFRACTION3485
2.7-2.7590.197504X-RAY DIFFRACTION3483
2.759-2.8230.179531X-RAY DIFFRACTION3485
2.823-2.8930.177533X-RAY DIFFRACTION3487
2.893-2.9720.198547X-RAY DIFFRACTION3486
2.972-3.0590.173537X-RAY DIFFRACTION3487
3.059-3.1580.183549X-RAY DIFFRACTION3487
3.158-3.2710.154524X-RAY DIFFRACTION3486
3.271-3.4020.149563X-RAY DIFFRACTION3489
3.402-3.5560.134548X-RAY DIFFRACTION3487
3.556-3.7440.124540X-RAY DIFFRACTION3489
3.744-3.9780.128564X-RAY DIFFRACTION3488
3.978-4.2860.114536X-RAY DIFFRACTION3486
4.286-4.7170.123547X-RAY DIFFRACTION3487
4.717-5.3990.118549X-RAY DIFFRACTION3488
5.399-6.8010.16573X-RAY DIFFRACTION3490
6.801-71.6380.173540X-RAY DIFFRACTION3482

+
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://pdbjlvh1.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