[English] 日本語
Yorodumi
- PDB-2b7d: Factor VIIa Inhibitors: Chemical Optimization, Preclinical Pharma... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2b7d
TitleFactor VIIa Inhibitors: Chemical Optimization, Preclinical Pharmacokinetics, Pharmacodynamics, and Efficacy in a Baboon Thrombosis Model
Components
  • (Coagulation factor VII) x 2
  • Tissue factor
KeywordsBLOOD CLOTTING / short hydrogen bond
Function / homology
Function and homology information


activation of plasma proteins involved in acute inflammatory response / activation of blood coagulation via clotting cascade / coagulation factor VIIa / response to Thyroid stimulating hormone / response to astaxanthin / response to thyrotropin-releasing hormone / response to 2,3,7,8-tetrachlorodibenzodioxine / response to carbon dioxide / response to genistein / serine-type peptidase complex ...activation of plasma proteins involved in acute inflammatory response / activation of blood coagulation via clotting cascade / coagulation factor VIIa / response to Thyroid stimulating hormone / response to astaxanthin / response to thyrotropin-releasing hormone / response to 2,3,7,8-tetrachlorodibenzodioxine / response to carbon dioxide / response to genistein / serine-type peptidase complex / response to vitamin K / positive regulation of platelet-derived growth factor receptor signaling pathway / positive regulation of leukocyte chemotaxis / response to thyroxine / NGF-stimulated transcription / response to cholesterol / cytokine receptor activity / response to growth hormone / positive regulation of positive chemotaxis / Extrinsic Pathway of Fibrin Clot Formation / positive regulation of endothelial cell apoptotic process / positive regulation of blood coagulation / animal organ regeneration / positive regulation of TOR signaling / Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus / Gamma-carboxylation of protein precursors / Removal of aminoterminal propeptides from gamma-carboxylated proteins / positive regulation of endothelial cell proliferation / serine-type peptidase activity / BMAL1:CLOCK,NPAS2 activates circadian expression / positive regulation of interleukin-8 production / circadian rhythm / phospholipid binding / protein processing / Golgi lumen / response to estrogen / cytokine-mediated signaling pathway / positive regulation of angiogenesis / blood coagulation / response to estradiol / : / protease binding / vesicle / response to hypoxia / positive regulation of cell migration / endoplasmic reticulum lumen / signaling receptor binding / external side of plasma membrane / serine-type endopeptidase activity / calcium ion binding / positive regulation of gene expression / cell surface / extracellular space / extracellular region / membrane / plasma membrane
Similarity search - Function
Tissue factor / Tissue factor, conserved site / Tissue factor signature. / Interferon/interleukin receptor domain / Interferon-alpha/beta receptor, fibronectin type III / : / Tissue factor / Peptidase S1A, coagulation factor VII/IX/X/C/Z / : / Coagulation factor-like, Gla domain superfamily ...Tissue factor / Tissue factor, conserved site / Tissue factor signature. / Interferon/interleukin receptor domain / Interferon-alpha/beta receptor, fibronectin type III / : / Tissue factor / Peptidase S1A, coagulation factor VII/IX/X/C/Z / : / Coagulation factor-like, Gla domain superfamily / Laminin / Laminin / Coagulation Factor Xa inhibitory site / EGF-like domain / EGF-type aspartate/asparagine hydroxylation site / EGF-like calcium-binding, conserved site / Calcium-binding EGF-like domain signature. / Aspartic acid and asparagine hydroxylation site. / EGF-like calcium-binding domain / Calcium-binding EGF-like 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. / Epidermal growth factor-like domain. / EGF-like domain profile. / EGF-like domain signature 1. / EGF-like domain signature 2. / EGF-like domain / Fibronectin type III / Fibronectin type III superfamily / Ribbon / 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 / Immunoglobulin-like fold / Peptidase S1, PA clan, chymotrypsin-like fold / Immunoglobulins / Peptidase S1, PA clan / Beta Barrel / Immunoglobulin-like / Sandwich / Mainly Beta
Similarity search - Domain/homology
Chem-C1B / Coagulation factor VII / Tissue factor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.24 Å
AuthorsYoung, W.B. / Mordenti, J. / Torkelson, S. / Shrader, W.D. / Kolesnikov, A. / Rai, R. / Liu, L. / Hu, H. / Leahy, E.M. / Green, M.J. ...Young, W.B. / Mordenti, J. / Torkelson, S. / Shrader, W.D. / Kolesnikov, A. / Rai, R. / Liu, L. / Hu, H. / Leahy, E.M. / Green, M.J. / Sprengeler, P.A. / Katz, B.A. / Yu, C. / Janc, J.W. / Elrod, K.C. / Marzec, U.M. / Hanson, S.R.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2006
Title: Factor VIIa inhibitors: Chemical optimization, preclinical pharmacokinetics, pharmacodynamics, and efficacy in an arterial baboon thrombosis model.
Authors: Young, W.B. / Mordenti, J. / Torkelson, S. / Shrader, W.D. / Kolesnikov, A. / Rai, R. / Liu, L. / Hu, H. / Leahy, E.M. / Green, M.J. / Sprengeler, P.A. / Katz, B.A. / Yu, C. / Janc, J.W. / ...Authors: Young, W.B. / Mordenti, J. / Torkelson, S. / Shrader, W.D. / Kolesnikov, A. / Rai, R. / Liu, L. / Hu, H. / Leahy, E.M. / Green, M.J. / Sprengeler, P.A. / Katz, B.A. / Yu, C. / Janc, J.W. / Elrod, K.C. / Marzec, U.M. / Hanson, S.R.
History
DepositionOct 4, 2005Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 14, 2006Provider: repository / Type: Initial release
Revision 1.1May 1, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Version format compliance
Revision 1.3Oct 11, 2017Group: Refinement description / Category: software
Revision 1.4Aug 23, 2023Group: Advisory / Data collection ...Advisory / Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_remark / pdbx_initial_refinement_model / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_remark.text / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.5Oct 16, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature
Remark 600HETEROGEN NOTE THAT IN THE CRYSTAL A REACEMIC MIXTURE OF THE LIGAND C1B WAS USED. THE PHENOLATE ...HETEROGEN NOTE THAT IN THE CRYSTAL A REACEMIC MIXTURE OF THE LIGAND C1B WAS USED. THE PHENOLATE OXYGEN MAKES SHORT HYDROGEN BONDS WITH THE HYDROXYL GROUP OF SER195 AND A WATER.

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
L: Coagulation factor VII
H: Coagulation factor VII
T: Tissue factor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)70,4224
Polymers69,8903
Non-polymers5331
Water5,513306
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5670 Å2
ΔGint-16 kcal/mol
Surface area22020 Å2
MethodPISA
Unit cell
Length a, b, c (Å)78.70, 69.03, 78.19
Angle α, β, γ (deg.)90.0, 89.49, 90.0
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Coagulation factor VII / Serum prothrombin conversion accelerator / SPCA / Proconvertin / Eptacog alfa


Mass: 17046.975 Da / Num. of mol.: 1 / Fragment: light chain
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: F7 / Cell line (production host): HEK 293 / Production host: Homo sapiens (human) / References: UniProt: P08709
#2: Protein Coagulation factor VII / Serum prothrombin conversion accelerator / SPCA / Proconvertin / Eptacog alfa


Mass: 28103.256 Da / Num. of mol.: 1 / Fragment: heavy chain
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: F7 / Cell line (production host): HEK 293 / Production host: Homo sapiens (human) / References: UniProt: P08709, coagulation factor VIIa
#3: Protein Tissue factor / TF / Coagulation factor III / Thromboplastin / CD142 antigen


Mass: 24739.434 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: F3 / Production host: Escherichia coli (E. coli) / References: UniProt: P13726
#4: Chemical ChemComp-C1B / (2R)-2-[5-(5-CARBAMIMIDOYL-1H-BENZOIMIDAZOL-2-YL)-6,2'-DIHYDROXY-5'-UREIDOMETHYL-BIPHENYL-3-YL]-SUCCINIC ACID


Mass: 532.505 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C26H24N6O7
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 306 / 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: 3.04 Å3/Da / Density % sol: 59.51 %
Crystal growTemperature: 290 K / Method: vapor diffusion, hanging drop / pH: 7.2
Details: 0.1 M citrate, 16-18 % PEG 5K MME, pH 7.2, VAPOR DIFFUSION, HANGING DROP, temperature 290.0K

-
Data collection

DiffractionMean temperature: 110 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.1 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 4 / Detector: CCD / Date: Dec 14, 2002
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.15→50 Å / Num. all: 46733 / Num. obs: 46266 / % possible obs: 99 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Rmerge(I) obs: 0.11 / Net I/σ(I): 11.3
Reflection shellResolution: 2.15→2.19 Å / % possible all: 97.1

-
Processing

Software
NameVersionClassification
DENZOdata reduction
SCALEPACKdata scaling
X-sightmodel building
Accelrysmodel building
X-PLOR3.851refinement
X-SIGHTphasing
ACCELRYSphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1DAN

1dan


Resolution: 2.24→7 Å / Cross valid method: THROUGHOUT / σ(F): 0
RfactorNum. reflection% reflectionSelection details
Rfree0.289 3892 10 %RANDOM
Rwork0.247 ---
all0.25 38857 --
obs0.25 38857 --
Refinement stepCycle: LAST / Resolution: 2.24→7 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3888 0 39 306 4233
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONx_bond_d0.019
X-RAY DIFFRACTIONx_angle_deg3.98
X-RAY DIFFRACTIONx_dihedral_angle_d24.7

+
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