2ZZU

Human Factor VIIA-Tissue Factor Complexed with ethylsulfonamide-D-5-(3-carboxybenzyloxy)-Trp-Gln-p-aminobenzamidine

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.273 
  • R-Value Work: 0.221 

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Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history. 


Literature

Design and synthesis of peptidomimetic factor VIIa inhibitors

Shiraishi, T., Kadono, S., Haramura, M., Kodama, H., Ono, Y., Iikura, H., Esaki, T., Koga, T., Hattori, K., Watanabe, Y., Sakamoto, A., Yoshihashi, K., Kitazawa, T., Esaki, K., Ohta, M., Sato, H., Kozono, T.

(2010) Chem Pharm Bull (Tokyo) 58: 38-44

  • DOI: https://doi.org/10.1248/cpb.58.38
  • Primary Citation of Related Structures:  
    2ZZU

  • PubMed Abstract: 

    Selective factor VIIa-tissue factor complex (FVIIa/TF) inhibition is regarded as a promising target for developing new anticoagulant drugs. In previous reports, we described a S3 subsite found in the X-ray crystal structure of compound 2 that bound to FVIIa/soluble tissue factor (sTF). Based on the X-ray crystal structure information and with the aim of improving the inhibition activity for FVIIa/TF and selectivity against other serine proteases, we synthesized derivatives by introducing substituents at position 5 of the indole ring of compound 2. Among them, compound 16 showed high selectivity against other serine proteases. Contrary to our expectations, compound 16 did not occupy the S3-subsite; X-ray structure analysis revealed that compound 16 improved selectivity by forming hydrogen bonds with Gln217, Thr99 and Asn100.

    • Organizational Affiliation: 

    Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Japan. shiraishitky@chugai-pharm.co.jp


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Factor VII light chainA [auth L]152Homo sapiensMutation(s): 0 
Gene Names: F7
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
Factor VII heavy chainB [auth H]254Homo sapiensMutation(s): 0 
Gene Names: F7
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 
Gene Names: F3
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
359
Query on 359
Download Ideal Coordinates CCD File 
N [auth H]3-[[3-[(2R)-3-[[(2S)-5-amino-1-[(4-carbamimidoylphenyl)methylamino]-1,5-dioxo-pentan-2-yl]amino]-2-(ethylsulfonylamino)-3-oxo-propyl]-1H-indol-5-yl]oxymethyl]benzoic acid
C34 H39 N7 O8 S
UDNWHSWDIIAZDA-URLMMPGGSA-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],
O [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
359 PDBBind:  2ZZU IC50: 39 (nM) from 1 assay(s)
Binding MOAD:  2ZZU IC50: 39 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.273 
  • R-Value Work: 0.221 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 71.4α = 90
b = 82.22β = 90
c = 123.47γ = 90
Software Package:
Software NamePurpose
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-03-24
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2011-11-30
    Changes: Database references
  • Version 1.3: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Data collection, Derived calculations, Structure summary
  • Version 1.4: 2023-11-01
    Changes: Advisory, Data collection, Database references, Refinement description, Structure summary
  • Version 1.5: 2023-11-15
    Changes: Data collection