3GY3

A comparative study on the inhibition of bovine beta-trypsin by bis-benzamidines diminazene and pentamidine by X-ray crystallography and ITC


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.212 
  • R-Value Work: 0.175 
  • R-Value Observed: 0.177 

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Ligand Structure Quality Assessment 


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Literature

Structural binding evidence of the trypanocidal drugs Berenil and Pentacarinate active principles to a serine protease model.

Perilo, C.S.Pereira, M.T.Santoro, M.M.Nagem, R.A.

(2010) Int J Biol Macromol 46: 502-511

  • DOI: https://doi.org/10.1016/j.ijbiomac.2010.03.006
  • Primary Citation of Related Structures:  
    3GY2, 3GY3, 3GY4, 3GY5, 3GY6, 3GY7, 3GY8

  • PubMed Abstract: 

    Bovine trypsin is a model system for the serine protease class of enzymes, which is an important target for contemporary medicinal chemistry. Some structural and thermodynamic reports are available on its interaction with benzamidine-based compounds but no structural information is available so far on its binding modes to the active principles of the trypanocidal drugs Pentacarinate (pentamidine) and Berenil (diminazene). The crystallographic structures of bovine beta-trypsin in complex with the ligands were determined to a resolution of 1.57 A (diminazene) and 1.70 A (diminazene and pentamidine). The second benzamidine moieties in these inhibitors are bound to the enzyme in different hot spots and only few hydrogen bonds mediate these interactions. Thermodynamic parameters for the association of pentamidine with beta-trypsin reveal that this inhibitor has about 1.3-fold lower affinity than diminazene. Moreover its binding mode resembles other benzamidine-based compounds that assess the aryl binding pocket of the enzyme; however, with almost 2.5-fold higher affinity. This is the first structural evidence of the binding of Berenil and Pentacarinate active principles trypanocidal drugs to serine proteases.


  • Organizational Affiliation

    Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, Belo Horizonte, MG, CEP 31270-901, Brazil.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cationic trypsin223Bos taurusMutation(s): 0 
EC: 3.4.21.4
UniProt
Find proteins for P00760 (Bos taurus)
Explore P00760 
Go to UniProtKB:  P00760
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00760
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PNT
Query on PNT

Download Ideal Coordinates CCD File 
C [auth A]1,5-BIS(4-AMIDINOPHENOXY)PENTANE
C19 H24 N4 O2
XDRYMKDFEDOLFX-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
D [auth A]
E [auth A]
F [auth A]
G [auth A]
H [auth A]
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
CA
Query on CA

Download Ideal Coordinates CCD File 
B [auth A]CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
PNT Binding MOAD:  3GY3 Kd: 2360 (nM) from 1 assay(s)
PDBBind:  3GY3 Kd: 2360 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.212 
  • R-Value Work: 0.175 
  • R-Value Observed: 0.177 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.393α = 90
b = 53.393β = 90
c = 104.76γ = 120
Software Package:
Software NamePurpose
HKL-2000data collection
AMoREphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-03-23
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance