[English] 日本語
Yorodumi
- PDB-2vvc: Aminopyrrolidine Factor Xa inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2vvc
TitleAminopyrrolidine Factor Xa inhibitor
Components
  • ACTIVATED FACTOR XA HEAVY CHAIN
  • FACTOR X LIGHT CHAIN
KeywordsHYDROLASE / ZYMOGEN / PROTEASE / GLYCOPROTEIN / GAMMA-CARBOXYGLUTAMIC ACID / BLOOD CLOTTING / COAGULATION FACTOR / HYDROXYLATION / SERINE PROTEASE / EGF-LIKE DOMAIN
Function / homology
Function and homology information


coagulation factor Xa / Defective factor IX causes thrombophilia / Defective cofactor function of FVIIIa variant / Defective F9 variant does not activate FX / Extrinsic Pathway of Fibrin Clot Formation / positive regulation of TOR signaling / Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus / Gamma-carboxylation of protein precursors / Common Pathway of Fibrin Clot Formation / Removal of aminoterminal propeptides from gamma-carboxylated proteins ...coagulation factor Xa / Defective factor IX causes thrombophilia / Defective cofactor function of FVIIIa variant / Defective F9 variant does not activate FX / Extrinsic Pathway of Fibrin Clot Formation / positive regulation of TOR signaling / Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus / Gamma-carboxylation of protein precursors / Common Pathway of Fibrin Clot Formation / Removal of aminoterminal propeptides from gamma-carboxylated proteins / Intrinsic Pathway of Fibrin Clot Formation / phospholipid binding / Golgi lumen / blood coagulation / positive regulation of cell migration / endoplasmic reticulum lumen / external side of plasma membrane / serine-type endopeptidase activity / calcium ion binding / proteolysis / 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 1. / EGF-like domain signature 2. / EGF-like domain / 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 / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan / Beta Barrel / Mainly Beta
Similarity search - Domain/homology
Chem-LZF / Coagulation factor X
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 1.95 Å
AuthorsGroebke-Zbinden, K. / Banner, D.W. / Benz, J.M. / Blasco, F. / Decoret, G. / Himber, J. / Kuhn, B. / Panday, N. / Ricklin, F. / Risch, P. ...Groebke-Zbinden, K. / Banner, D.W. / Benz, J.M. / Blasco, F. / Decoret, G. / Himber, J. / Kuhn, B. / Panday, N. / Ricklin, F. / Risch, P. / Schlatter, D. / Stahl, M. / Unger, R. / Haap, W.
CitationJournal: Eur.J.Med.Chem. / Year: 2009
Title: Design of Novel Aminopyrrolidine Factor Xa Inhibitors from a Screening Hit.
Authors: Zbinden, K.G. / Anselm, L. / Banner, D.W. / Benz, J.M. / Blasco, F. / Decoret, G. / Himber, J. / Kuhn, B. / Panday, N. / Ricklin, F. / Risch, P. / Schlatter, D. / Stahl, M. / Thomi, S. / Unger, R. / Haap, W.
History
DepositionJun 5, 2008Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jul 7, 2009Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Refinement description / Version format compliance
Revision 1.2Jun 28, 2017Group: Data collection / Category: diffrn_source / Item: _diffrn_source.type
Revision 1.3Dec 13, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_initial_refinement_model / pdbx_struct_conn_angle / struct_conn / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_ptnr1_PDB_ins_code / _struct_conn.pdbx_ptnr2_PDB_ins_code / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.4Nov 20, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification
Remark 700 SHEET DETERMINATION METHOD: DSSP THE SHEETS PRESENTED AS "AA" IN EACH CHAIN ON SHEET RECORDS BELOW ... SHEET DETERMINATION METHOD: DSSP THE SHEETS PRESENTED AS "AA" IN EACH CHAIN ON SHEET RECORDS BELOW IS ACTUALLY AN 8-STRANDED BARREL THIS IS REPRESENTED BY A 9-STRANDED SHEET IN WHICH THE FIRST AND LAST STRANDS ARE IDENTICAL. THE SHEETS PRESENTED AS "BA" IN EACH CHAIN ON SHEET RECORDS BELOW IS ACTUALLY AN 7-STRANDED BARREL THIS IS REPRESENTED BY A 8-STRANDED SHEET IN WHICH THE FIRST AND LAST STRANDS ARE IDENTICAL. THE SHEETS PRESENTED AS "BB" IN EACH CHAIN ON SHEET RECORDS BELOW IS ACTUALLY AN 6-STRANDED BARREL THIS IS REPRESENTED BY A 7-STRANDED SHEET IN WHICH THE FIRST AND LAST STRANDS ARE IDENTICAL.

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: ACTIVATED FACTOR XA HEAVY CHAIN
B: ACTIVATED FACTOR XA HEAVY CHAIN
K: FACTOR X LIGHT CHAIN
L: FACTOR X LIGHT CHAIN
hetero molecules


Theoretical massNumber of molelcules
Total (without water)67,5649
Polymers66,4684
Non-polymers1,0965
Water10,341574
1
A: ACTIVATED FACTOR XA HEAVY CHAIN
L: FACTOR X LIGHT CHAIN
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,8025
Polymers33,2342
Non-polymers5683
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1910 Å2
ΔGint-35 kcal/mol
Surface area32210 Å2
MethodPISA
2
B: ACTIVATED FACTOR XA HEAVY CHAIN
K: FACTOR X LIGHT CHAIN
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,7624
Polymers33,2342
Non-polymers5282
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1900 Å2
ΔGint-22 kcal/mol
Surface area13090 Å2
MethodPISA
3
A: ACTIVATED FACTOR XA HEAVY CHAIN
hetero molecules


Theoretical massNumber of molelcules
Total (without water)27,7414
Polymers27,1731
Non-polymers5683
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
4
L: FACTOR X LIGHT CHAIN


Theoretical massNumber of molelcules
Total (without water)6,0611
Polymers6,0611
Non-polymers00
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
5
B: ACTIVATED FACTOR XA HEAVY CHAIN
hetero molecules


Theoretical massNumber of molelcules
Total (without water)27,7013
Polymers27,1731
Non-polymers5282
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
6
K: FACTOR X LIGHT CHAIN


Theoretical massNumber of molelcules
Total (without water)6,0611
Polymers6,0611
Non-polymers00
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)48.960, 77.190, 74.760
Angle α, β, γ (deg.)90.00, 92.12, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

-
Protein , 2 types, 4 molecules ABKL

#1: Protein ACTIVATED FACTOR XA HEAVY CHAIN


Mass: 27172.980 Da / Num. of mol.: 2 / Fragment: PEPTIDASE S1 DOMAIN, RESIDUES 235-475 / Mutation: YES
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Production host: ESCHERICHIA COLI (E. coli) / References: UniProt: P00742, coagulation factor Xa
#2: Protein FACTOR X LIGHT CHAIN


Mass: 6060.816 Da / Num. of mol.: 2 / Fragment: EGF2, RESIDUES 126-180
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Production host: ESCHERICHIA COLI (E. coli) / References: UniProt: P00742, coagulation factor Xa

-
Non-polymers , 4 types, 579 molecules

#3: Chemical ChemComp-LZF / 5-chloro-N-[(3S,4S)-1-(2-{[2-fluoro-4-(2-oxopyridin-1(2H)-yl)phenyl]amino}-2-oxoethyl)-4-methoxypyrrolidin-3-yl]thiophene-2-carboxamide


Mass: 504.962 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C23H22ClFN4O4S
#4: Chemical ChemComp-CA / CALCIUM ION


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


Mass: 22.990 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Na
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 574 / Source method: isolated from a natural source / Formula: H2O

-
Details

Compound detailsENGINEERED RESIDUE IN CHAIN A, ARG 372 TO GLU ENGINEERED RESIDUE IN CHAIN B, ARG 372 TO GLU
Has protein modificationY
Sequence detailsARG-GLU MUTANT.THE RESIDUE NUMBERING IN THE CATALYTIC DOMAIN FOLLOWS THAT OF CHYMOTRYPSINOGEN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.26 Å3/Da / Density % sol: 45.6 % / Description: ICE RING AT 2.26A EXCLUDED

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: ENRAF-NONIUS FR591 / Wavelength: 1.5418
DetectorType: MARRESEARCH / Detector: IMAGE PLATE / Date: Dec 10, 2004 / Details: OSMIC MIRRORS
RadiationMonochromator: OSMIC MIRRORS / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 1.95→50 Å / Num. obs: 36457 / % possible obs: 90.3 % / Observed criterion σ(I): -3 / Redundancy: 3.66 % / Biso Wilson estimate: 28 Å2 / Rmerge(I) obs: 0.12 / Net I/σ(I): 7.84
Reflection shellResolution: 1.95→2.07 Å / Redundancy: 3.54 % / Rmerge(I) obs: 0.38 / Mean I/σ(I) obs: 3.03 / % possible all: 95.9

-
Processing

Software
NameVersionClassification
REFMAC5.4.0067refinement
XDSdata reduction
XDSdata scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 2BOK

2bok


Resolution: 1.95→74.74 Å / Cor.coef. Fo:Fc: 0.934 / Cor.coef. Fo:Fc free: 0.878 / SU B: 10.508 / SU ML: 0.16 / TLS residual ADP flag: UNVERIFIED / Cross valid method: THROUGHOUT / ESU R: 0.24 / ESU R Free: 0.213 / Stereochemistry target values: MAXIMUM LIKELIHOOD
RfactorNum. reflection% reflectionSelection details
Rfree0.275 1849 5.1 %RANDOM
Rwork0.199 ---
obs0.203 34654 95.1 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 13.43 Å2
Baniso -1Baniso -2Baniso -3
1-0.11 Å20 Å2-0.76 Å2
2--0.38 Å20 Å2
3----0.54 Å2
Refinement stepCycle: LAST / Resolution: 1.95→74.74 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4396 0 71 574 5041
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0120.0224619
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.4871.9646240
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.1725564
X-RAY DIFFRACTIONr_dihedral_angle_2_deg31.48924.028211
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.76915793
X-RAY DIFFRACTIONr_dihedral_angle_4_deg13.3291530
X-RAY DIFFRACTIONr_chiral_restr0.0930.2665
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.0213502
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it0.6441.52801
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it1.14624503
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it1.82431818
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it2.6064.51737
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 1.95→2 Å / Total num. of bins used: 20 /
RfactorNum. reflection
Rfree0.344 143
Rwork0.241 2590
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)
13.2593-0.5458-0.36441.5876-1.15293.855-0.0192-0.4098-0.04170.12220.06990.0585-0.1336-0.1593-0.0507-0.1846-0.02130.0385-0.14480.0402-0.1055-9.329-8.07151.177
22.91260.03470.36861.47240.08641.2317-0.05090.30150.0697-0.16190.03570.033-0.05640.00940.0152-0.1509-0.01550.0254-0.17270.0197-0.17023.0251.08932.343
30.97170.72480.451.59230.51020.27280.06760.0613-0.02510.07050.0231-0.0939-0.03910.1005-0.0906-0.1620.01790.0246-0.0444-0.0411-0.101429.96221.12115.515
42.05130.3052-0.03051.31840.05911.9382-0.07060.1461-0.1386-0.20660.03740.07030.1529-0.1210.0332-0.0453-0.00470.0175-0.1245-0.0173-0.119218.43814.397-4.172
510.5866-7.80279.3876.1561-7.53859.27150.4323-0.20030.6824-1.0109-0.46691.2870.6819-0.0470.03460.0196-0.03170.0562-0.0078-0.132-0.0036.57511.218-9.219
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1L87 - 138
2X-RAY DIFFRACTION2A16 - 243
3X-RAY DIFFRACTION3A1244
4X-RAY DIFFRACTION3K87 - 139
5X-RAY DIFFRACTION4B16 - 243
6X-RAY DIFFRACTION5B1244

+
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