[English] 日本語
Yorodumi
- PDB-4x8v: FACTOR VIIA IN COMPLEX WITH THE INHIBITOR (methyl {3-[(2R)-1-{(2R... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4x8v
TitleFACTOR VIIA IN COMPLEX WITH THE INHIBITOR (methyl {3-[(2R)-1-{(2R)-2-(3,4-dimethoxyphenyl)-2-[(1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl)amino]acetyl}pyrrolidin-2-yl]-4-(propan-2-ylsulfonyl)phenyl}carbamate)
Components
  • Factor VIIa (Heavy Chain)
  • Factor VIIa (Light Chain)
KeywordsHYDROLASE/HYDROLASE INHIBITOR / GLYCOPROTEIN / HYDROLASE / SERINE PROTEASE / PLASMA / BLOOD COAGULATION FACTOR / PROTEIN INHIBITOR COMPLEX / CALCIUM- BINDING / HYDROLASE-HYDROLASE INHIBITOR complex
Function / homology
Function and homology information


coagulation factor VIIa / response to Thyroid stimulating hormone / response to 2,3,7,8-tetrachlorodibenzodioxine / response to astaxanthin / response to thyrotropin-releasing hormone / response to genistein / serine-type peptidase complex / positive regulation of platelet-derived growth factor receptor signaling pathway / response to vitamin K / response to carbon dioxide ...coagulation factor VIIa / response to Thyroid stimulating hormone / response to 2,3,7,8-tetrachlorodibenzodioxine / response to astaxanthin / response to thyrotropin-releasing hormone / response to genistein / serine-type peptidase complex / positive regulation of platelet-derived growth factor receptor signaling pathway / response to vitamin K / response to carbon dioxide / response to thyroxine / positive regulation of leukocyte chemotaxis / response to cholesterol / response to growth hormone / positive regulation of positive chemotaxis / Extrinsic Pathway of Fibrin Clot Formation / positive regulation of TOR signaling / positive regulation of blood coagulation / animal organ regeneration / Gamma-carboxylation of protein precursors / Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus / Removal of aminoterminal propeptides from gamma-carboxylated proteins / serine-type peptidase activity / BMAL1:CLOCK,NPAS2 activates circadian gene expression / protein processing / Golgi lumen / response to estrogen / circadian rhythm / blood coagulation / response to estradiol / collagen-containing extracellular matrix / vesicle / response to hypoxia / positive regulation of cell migration / endoplasmic reticulum lumen / serine-type endopeptidase activity / signaling receptor binding / calcium ion binding / extracellular space / extracellular region / plasma membrane
Similarity search - Function
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. ...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 2. / EGF-like domain signature 1. / EGF-like domain / Ribbon / 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 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-3Z9 / Coagulation factor VII
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.5 Å
AuthorsWei, A.
CitationJournal: J.Med.Chem. / Year: 2015
Title: Discovery of Novel P1 Groups for Coagulation Factor VIIa Inhibition Using Fragment-Based Screening.
Authors: Cheney, D.L. / Bozarth, J.M. / Metzler, W.J. / Morin, P.E. / Mueller, L. / Newitt, J.A. / Nirschl, A.H. / Rendina, A.R. / Tamura, J.K. / Wei, A. / Wen, X. / Wurtz, N.R. / Seiffert, D.A. / ...Authors: Cheney, D.L. / Bozarth, J.M. / Metzler, W.J. / Morin, P.E. / Mueller, L. / Newitt, J.A. / Nirschl, A.H. / Rendina, A.R. / Tamura, J.K. / Wei, A. / Wen, X. / Wurtz, N.R. / Seiffert, D.A. / Wexler, R.R. / Priestley, E.S.
History
DepositionDec 10, 2014Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 25, 2015Provider: repository / Type: Initial release
Revision 1.1Apr 8, 2015Group: Database references
Revision 1.2Oct 16, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description / Source and taxonomy / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / citation / database_2 / entity_src_gen / pdbx_entry_details / pdbx_initial_refinement_model / pdbx_modification_feature / pdbx_struct_assembly / pdbx_struct_assembly_gen / pdbx_struct_assembly_prop / pdbx_struct_oper_list / struct_keywords
Item: _citation.journal_id_CSD / _database_2.pdbx_DOI ..._citation.journal_id_CSD / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _entity_src_gen.pdbx_alt_source_flag / _pdbx_struct_assembly.oligomeric_details / _pdbx_struct_assembly_gen.asym_id_list / _pdbx_struct_assembly_prop.type / _pdbx_struct_assembly_prop.value / _pdbx_struct_oper_list.symmetry_operation / _struct_keywords.text

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
H: Factor VIIa (Heavy Chain)
L: Factor VIIa (Light Chain)
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,3119
Polymers34,1342
Non-polymers1,1777
Water2,522140
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3350 Å2
ΔGint-71 kcal/mol
Surface area13440 Å2
MethodPISA
Unit cell
Length a, b, c (Å)95.300, 95.300, 116.300
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number92
Space group name H-MP41212
Components on special symmetry positions
IDModelComponents
11H-422-

HOH

Detailschains H & L

-
Components

-
Protein , 2 types, 2 molecules HL

#1: Protein Factor VIIa (Heavy Chain) / Proconvertin / Serum prothrombin conversion accelerator / SPCA


Mass: 28103.256 Da / Num. of mol.: 1 / Fragment: UNP RESIDUES 213-466
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: F7 / Production host: Cricetinae (hamsters) / References: UniProt: P08709, coagulation factor VIIa
#2: Protein Factor VIIa (Light Chain) / Proconvertin / Serum prothrombin conversion accelerator / SPCA


Mass: 6030.827 Da / Num. of mol.: 1 / Fragment: UNP RESIDUES 150-204
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: F7 / Production host: Cricetinae (hamsters) / References: UniProt: P08709, coagulation factor VIIa

-
Non-polymers , 5 types, 147 molecules

#3: Chemical ChemComp-3Z9 / methyl {3-[(2R)-1-{(2R)-2-(3,4-dimethoxyphenyl)-2-[(1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl)amino]acetyl}pyrrolidin-2-yl]-4-(propan-2-ylsulfonyl)phenyl}carbamate


Mass: 664.768 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C34H40N4O8S
#4: Chemical ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Ca
#5: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: SO4
#6: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C3H8O3
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 140 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.87 Å3/Da / Density % sol: 68.2 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 6
Details: 100 mM MES, pH 6.0, 20 mM CACL2, 17.5%(W/V) PEG 6000

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 210 / Detector: CCD / Date: Nov 11, 2006
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.5→50 Å / Num. obs: 18122 / % possible obs: 94.4 % / Observed criterion σ(I): 0 / Redundancy: 8.4 % / Biso Wilson estimate: 42.4 Å2 / Rmerge(I) obs: 0.109 / Net I/σ(I): 22.7
Reflection shellResolution: 2.5→2.59 Å / Redundancy: 8.5 % / Rmerge(I) obs: 0.39 / Mean I/σ(I) obs: 4.9 / Rejects: 0 / % possible all: 94

-
Processing

Software
NameVersionClassification
BUSTER-TNTBUSTER 2.11.5refinement
PDB_EXTRACT3.15data extraction
HKL-2000data reduction
HKL-2000data scaling
AMoREphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: FACTOR VIIA/LIGAND

Resolution: 2.5→44.02 Å / Cor.coef. Fo:Fc: 0.9181 / Cor.coef. Fo:Fc free: 0.8929 / SU R Cruickshank DPI: 0.335 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.365 / SU Rfree Blow DPI: 0.245 / SU Rfree Cruickshank DPI: 0.239
RfactorNum. reflection% reflectionSelection details
Rfree0.2297 1607 9.8 %RANDOM
Rwork0.1931 ---
obs0.1968 16398 85.65 %-
Displacement parametersBiso max: 119.24 Å2 / Biso mean: 30.77 Å2 / Biso min: 6.95 Å2
Baniso -1Baniso -2Baniso -3
1-4.1884 Å20 Å20 Å2
2--4.1884 Å20 Å2
3----8.3769 Å2
Refine analyzeLuzzati coordinate error obs: 0.296 Å
Refinement stepCycle: final / Resolution: 2.5→44.02 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2368 0 75 140 2583
Biso mean--39.29 29.67 -
Num. residues----309
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d845SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes51HARMONIC2
X-RAY DIFFRACTIONt_gen_planes404HARMONIC5
X-RAY DIFFRACTIONt_it2546HARMONIC20
X-RAY DIFFRACTIONt_nbd0SEMIHARMONIC5
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion312SEMIHARMONIC5
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_contact2899SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d2546HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg3507HARMONIC21.19
X-RAY DIFFRACTIONt_omega_torsion3.56
X-RAY DIFFRACTIONt_other_torsion16.68
LS refinement shellResolution: 2.5→2.67 Å / Total num. of bins used: 8
RfactorNum. reflection% reflection
Rfree0.2884 270 10.28 %
Rwork0.231 2356 -
all0.237 2626 -
obs--85.65 %

+
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