[English] 日本語
Yorodumi
- PDB-4zae: Development of a novel class of potent and selective FIXa inhibitors -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4zae
TitleDevelopment of a novel class of potent and selective FIXa inhibitors
Components(Coagulation factor ...) x 2
KeywordsHydrolase/Hydrolase Inhibitor / SERINE PROTEINASE / BLOOD COAGULATION / COAGULATION FACTOR / Hydrolase-Hydrolase Inhibitor complex
Function / homology
Function and homology information


Defective F9 secretion / Defective gamma-carboxylation of F9 / coagulation factor IXa / Defective F9 activation / Defective factor IX causes thrombophilia / Defective cofactor function of FVIIIa variant / Defective F9 variant does not activate FX / zymogen activation / Extrinsic Pathway of Fibrin Clot Formation / Protein hydroxylation ...Defective F9 secretion / Defective gamma-carboxylation of F9 / coagulation factor IXa / Defective F9 activation / Defective factor IX causes thrombophilia / Defective cofactor function of FVIIIa variant / Defective F9 variant does not activate FX / zymogen activation / Extrinsic Pathway of Fibrin Clot Formation / Protein hydroxylation / 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 / Intrinsic Pathway of Fibrin Clot Formation / Golgi lumen / blood coagulation / collagen-containing extracellular matrix / endopeptidase activity / endoplasmic reticulum lumen / serine-type endopeptidase activity / calcium ion binding / proteolysis / extracellular space / extracellular exosome / extracellular region / metal ion binding / 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-4M1 / Coagulation factor IX
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.86 Å
AuthorsHruza, A. / Reichert, P.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2015
Title: Development of a novel class of potent and selective FIXa inhibitors.
Authors: Zhang, T. / Andre, P. / Bateman, T.J. / Chen, Y.H. / Desai, K. / Ellsworth, K. / Geissler, W.M. / Guo, L. / Hruza, A. / Jian, T. / Meng, D. / Parker, D.L. / Qian, X. / Reichert, P. / Sherer, ...Authors: Zhang, T. / Andre, P. / Bateman, T.J. / Chen, Y.H. / Desai, K. / Ellsworth, K. / Geissler, W.M. / Guo, L. / Hruza, A. / Jian, T. / Meng, D. / Parker, D.L. / Qian, X. / Reichert, P. / Sherer, E.C. / Shu, M. / Smith, C.J. / Sonatore, L.M. / Tschirret-Guth, R. / Nolting, A.F. / Orr, R. / Campeau, L.C. / Araki, K. / Nishimura, T. / Sakurada, I. / Wood, H.B.
History
DepositionApr 13, 2015Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 3, 2015Provider: repository / Type: Initial release
Revision 1.1Oct 28, 2015Group: Database references
Revision 1.2Nov 22, 2017Group: Database references / Derived calculations / Refinement description
Category: citation / pdbx_struct_oper_list / software
Item: _citation.journal_id_CSD / _pdbx_struct_oper_list.symmetry_operation / _software.classification
Revision 1.3Sep 27, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / diffrn_radiation_wavelength / pdbx_initial_refinement_model / software
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _software.name
Revision 1.4Oct 16, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Coagulation factor IX
B: Coagulation factor IX
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,6825
Polymers32,9472
Non-polymers7363
Water4,684260
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1570 Å2
ΔGint-10 kcal/mol
Surface area13650 Å2
MethodPISA
Unit cell
Length a, b, c (Å)99.452, 99.452, 94.737
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number146
Space group name H-MH3

-
Components

-
Coagulation factor ... , 2 types, 2 molecules AB

#1: Protein Coagulation factor IX / Christmas factor / Plasma thromboplastin component / PTC


Mass: 26104.703 Da / Num. of mol.: 1 / Fragment: Peptidase S1 domain (UNP residues 227-461) / Mutation: R150A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: F9 / Production host: Escherichia coli (E. coli) / References: UniProt: P00740, coagulation factor IXa
#2: Protein Coagulation factor IX / Christmas factor / Plasma thromboplastin component / PTC


Mass: 6841.809 Da / Num. of mol.: 1 / Fragment: EG-like 2 domain (UNP residues 131-191)
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: F9 / Production host: Escherichia coli (E. coli) / References: UniProt: P00740, coagulation factor IXa

-
Non-polymers , 4 types, 263 molecules

#3: Chemical ChemComp-4M1 / 2,6-dichloro-N-[(2R)-2-(5,6-dimethyl-1H-benzimidazol-2-yl)-2-phenylethyl]-4-(4H-1,2,4-triazol-4-yl)benzamide


Mass: 505.398 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C26H22Cl2N6O
#4: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Na
#5: Chemical ChemComp-NHE / 2-[N-CYCLOHEXYLAMINO]ETHANE SULFONIC ACID / N-CYCLOHEXYLTAURINE / CHES


Mass: 207.290 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C8H17NO3S / Comment: pH buffer*YM
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 260 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION

-
Sample preparation

CrystalDensity Matthews: 2.82 Å3/Da / Density % sol: 56.33 %
Crystal growTemperature: 295 K / Method: vapor diffusion, hanging drop / pH: 9
Details: 50 mM CHES, pH 9.0, 1.3 M tri-sodium citrate and 3 mM compound (cross seeded with crystals grown from 50 mM Tris, pH 7.2, 1.45 M ammonium sulfate, 2.0 M sodium chloride and 3 mM compound)

-
Data collection

DiffractionMean temperature: 95 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Apr 24, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.857→63.728 Å / Num. obs: 29508 / % possible obs: 100 % / Redundancy: 5.2 % / Biso Wilson estimate: 24.32 Å2 / Rmerge(I) obs: 0.078 / Rsym value: 0.078 / Net I/σ(I): 14.8
Reflection shellResolution: 1.857→1.863 Å / Redundancy: 4.8 % / Rmerge(I) obs: 0.575 / Mean I/σ(I) obs: 0.575 / % possible all: 100

-
Processing

Software
NameVersionClassification
XDS(VERSION December 29data reduction
SCALAdata scaling
MOLREPphasing
BUSTER2.11.4refinement
Cootmodel building
autoPROCdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1RFN

1rfn


Resolution: 1.86→63.7 Å / Cor.coef. Fo:Fc: 0.9646 / Cor.coef. Fo:Fc free: 0.9546 / SU R Cruickshank DPI: 0.138 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.099 / SU Rfree Blow DPI: 0.094 / SU Rfree Cruickshank DPI: 0.095
RfactorNum. reflection% reflectionSelection details
Rfree0.1741 1475 5.02 %RANDOM
Rwork0.1477 ---
obs0.149 29369 99.98 %-
Displacement parametersBiso mean: 32.41 Å2
Baniso -1Baniso -2Baniso -3
1--1.0361 Å20 Å20 Å2
2---1.0361 Å20 Å2
3---2.0722 Å2
Refine analyzeLuzzati coordinate error obs: 0.193 Å
Refinement stepCycle: LAST / Resolution: 1.86→63.7 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4453 0 49 260 4762
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.014602HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.088304HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d991SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes56HARMONIC2
X-RAY DIFFRACTIONt_gen_planes738HARMONIC5
X-RAY DIFFRACTIONt_it4602HARMONIC20
X-RAY DIFFRACTIONt_nbd4SEMIHARMONIC5
X-RAY DIFFRACTIONt_omega_torsion4.26
X-RAY DIFFRACTIONt_other_torsion13.63
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion299SEMIHARMONIC5
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_contact5054SEMIHARMONIC4
LS refinement shellResolution: 1.86→1.93 Å / Total num. of bins used: 15
RfactorNum. reflection% reflection
Rfree0.194 155 5.37 %
Rwork0.1865 2729 -
all0.1869 2884 -
obs--99.98 %
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)
11.32720.515-0.37431.5309-0.51582.1672-0.1630.1004-0.1161-0.22530.07640.01070.4164-0.00060.08670.0193-0.00140.0285-0.1265-0.0058-0.1313-3.4237-33.678-3.2478
21.0688-0.0410.47181.5175-0.69831.7873-0.0313-0.11360.07830.1096-0.1052-0.03-0.16260.21360.13650.00570.0041-0.01540.02460.0083-0.06515.8375-28.472419.8828
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1{ A|* }
2X-RAY DIFFRACTION2{ B|* }

+
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