1WUN

Human Factor Viia-Tissue Factor Complexed with ethylsulfonamide-D-Trp-Gln-p-aminobenzamidine


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.264 
  • R-Value Work: 0.217 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Structure-based design of P3 moieties in the peptide mimetic factor VIIa inhibitor

Kadono, S.Sakamoto, A.Kikuchi, Y.Oh-eda, M.Yabuta, N.Yoshihashi, K.Kitazawa, T.Suzuki, T.Koga, T.Hattori, K.Shiraishi, T.Haramura, M.Kodama, H.Ono, Y.Esaki, T.Sato, H.Watanabe, Y.Itoh, S.Ohta, M.Kozono, T.

(2005) Biochem Biophys Res Commun 327: 589-596

  • DOI: https://doi.org/10.1016/j.bbrc.2004.12.042
  • Primary Citation of Related Structures:  
    1WUN, 1WV7

  • PubMed Abstract: 

    Selective factor VIIa-tissue factor complex (FVIIa/TF) inhibition is seen as a promising target for developing new anticoagulant drugs. Structure-based designs of the P3 moiety in the peptide mimetic factor VIIa inhibitor successfully lead to novel inhibitors with selectivity for FVIIa/TF and extrinsic coagulation the same as or even higher than those of previously reported peptide mimetic factor VIIa inhibitors. X-ray crystal structure analysis reveals that one of the novel inhibitors shows improved selectivity by forming interactions between the inhibitor and FVIIa as expected. Another of the novel inhibitors achieves improved selectivity through an unexpected hydrogen bond with Gln217, with a unique bent conformation in FVIIa/TF accompanied by conformational changes of the inhibitor and the protein.


  • Organizational Affiliation

    Fuji Gotemba Research Labs, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan. kadonosuj@chugai-pharm.co.jp


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Coagulation factor VIIA [auth L]152Homo sapiensMutation(s): 10 
EC: 3.4.21.21
UniProt & NIH Common Fund Data Resources
Find proteins for P08709 (Homo sapiens)
Explore P08709 
Go to UniProtKB:  P08709
PHAROS:  P08709
GTEx:  ENSG00000057593 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP08709
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Coagulation factor VIIB [auth H]254Homo sapiensMutation(s): 0 
EC: 3.4.21.21
UniProt & NIH Common Fund Data Resources
Find proteins for P08709 (Homo sapiens)
Explore P08709 
Go to UniProtKB:  P08709
PHAROS:  P08709
GTEx:  ENSG00000057593 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP08709
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Tissue factorC [auth T]218Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P13726 (Homo sapiens)
Explore P13726 
Go to UniProtKB:  P13726
PHAROS:  P13726
GTEx:  ENSG00000117525 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP13726
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
P5B
Query on P5B

Download Ideal Coordinates CCD File 
O [auth H]N-(ETHYLSULFONYL)TRYPTOPHYL-N~1~-{4-[AMINO(IMINO)METHYL]BENZYL}GLUTAMAMIDE
C26 H33 N7 O5 S
FJGWLOKDOKYXMU-FCHUYYIVSA-N
BGC
Query on BGC

Download Ideal Coordinates CCD File 
D [auth L]beta-D-glucopyranose
C6 H12 O6
WQZGKKKJIJFFOK-VFUOTHLCSA-N
FUC
Query on FUC

Download Ideal Coordinates CCD File 
E [auth L]alpha-L-fucopyranose
C6 H12 O5
SHZGCJCMOBCMKK-SXUWKVJYSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
F [auth L]
G [auth L]
H [auth L]
I [auth L]
J [auth L]
F [auth L],
G [auth L],
H [auth L],
I [auth L],
J [auth L],
K [auth L],
L,
M [auth L],
N [auth H]
CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
CGU
Query on CGU
A [auth L]L-PEPTIDE LINKINGC6 H9 N O6GLU
Binding Affinity Annotations 
IDSourceBinding Affinity
P5B Binding MOAD:  1WUN IC50: 62 (nM) from 1 assay(s)
PDBBind:  1WUN IC50: 62 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.264 
  • R-Value Work: 0.217 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 71.29α = 90
b = 82.53β = 90
c = 123.53γ = 90
Software Package:
Software NamePurpose
CNXrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2005-12-08
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Database references, Derived calculations, Structure summary
  • Version 1.4: 2023-10-25
    Changes: Data collection, Database references, Refinement description, Structure summary
  • Version 1.5: 2023-11-15
    Changes: Data collection