The 3-dimensional structure of trypanothione reductase from Trypanosoma cruzi as a basis for drug design against Chagas' disease

1994 ◽  
pp. 545-556
Keyword(s):  
Drug Design ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Dimensional Structure ◽  
Trypanothione Reductase ◽  
3 Dimensional

scholarly journals Cruzain structures: apocruzain and cruzain bound to S-methyl thiomethanesulfonate and implications for drug design

2019 ◽  
Vol 75 (6) ◽  
pp. 419-427 ◽  
Author(s):  
Elany Barbosa da Silva ◽  
Elfriede Dall ◽  
Peter Briza ◽  
Hans Brandstetter ◽  
Rafaela Salgado Ferreira
Keyword(s):  
Drug Design ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Cysteine Protease ◽  
In Silico ◽  
Structural Information ◽  
Mass Spectrometric ◽  
Catalytic Cysteine ◽  
Reversible Covalent ◽  
Covalent Inhibitor

Chagas disease, which is caused by Trypanosoma cruzi, affects more than six million people worldwide. Cruzain is the major cysteine protease involved in the survival of this parasite. Here, the expression, purification and crystallization of this enzyme are reported. The cruzain crystals diffracted to 1.2 Å resolution, yielding two novel cruzain structures: apocruzain and cruzain bound to the reversible covalent inhibitor S-methyl thiomethanesulfonate. Mass-spectrometric experiments confirmed the presence of a methylthiol group attached to the catalytic cysteine. Comparison of these structures with previously published structures indicates the rigidity of the cruzain structure. These results provide further structural information about the enzyme and may help in new in silico studies to identify or optimize novel prototypes of cruzain inhibitors.

Rational Drug Design

2014 ◽  
Vol 4 (1) ◽  
pp. 59-85 ◽  
Author(s):  
Khaled H. Barakat ◽  
Michael Houghton ◽  
D. Lorne Tyrrel ◽  
Jack A. Tuszynski
Keyword(s):  
Drug Design ◽  
Rational Drug Design ◽  
Dimensional Structure ◽  
Computational Tools ◽  
Structure Based Drug Design ◽  
Practical Applications ◽  
3 Dimensional ◽  
Drug Candidates ◽  
The Past ◽  
Rational Drug

For the past three decades rationale drug design (RDD) has been developing as an innovative, rapid and successful way to discover new drug candidates. Many strategies have been followed and several targets with diverse structures and different biological roles have been investigated. Despite the variety of computational tools available, one can broadly divide them into two major classes that can be adopted either separately or in combination. The first class involves structure-based drug design, when the target's 3-dimensional structure is available or it can be computationally generated using homology modeling. On the other hand, when only a set of active molecules is available, and the structure of the target is unknown, ligand-based drug design tools are usually used. This review describes some recent advances in rational drug design, summarizes a number of their practical applications, and discusses both the advantages and shortcomings of the various techniques used.

scholarly journals Rational Drug Design Rational Drug Design

2017 ◽  
pp. 1144-1174
Author(s):  
Khaled H. Barakat ◽  
Michael Houghton ◽  
D. Lorne Tyrrel ◽  
Jack A. Tuszynski
Keyword(s):  
Drug Design ◽  
Rational Drug Design ◽  
The Other ◽  
Dimensional Structure ◽  
Design Tools ◽  
Structure Based Drug Design ◽  
Practical Applications ◽  
3 Dimensional ◽  
Drug Candidates ◽  
Rational Drug

For the past three decades rationale drug design (RDD) has been developing as an innovative, rapid and successful way to discover new drug candidates. Many strategies have been followed and several targets with diverse structures and different biological roles have been investigated. Despite the variety of computational tools available, one can broadly divide them into two major classes that can be adopted either separately or in combination. The first class involves structure-based drug design, when the target's 3-dimensional structure is available or it can be computationally generated using homology modeling. On the other hand, when only a set of active molecules is available, and the structure of the target is unknown, ligand-based drug design tools are usually used. This review describes some recent advances in rational drug design, summarizes a number of their practical applications, and discusses both the advantages and shortcomings of the various techniques used.

scholarly journals Crystallization and preliminary crystallographic analysis of trypanothione reductase from Trypanosoma cruzi , the causative agent of Chagas' disease

FEBS Letters ◽  
1993 ◽  
Vol 317 (1-2) ◽  
pp. 105-108 ◽  
Author(s):  
R.Luise Krauth-Siegel ◽  
Christian Sticherling ◽  
Ingrid Jöst ◽  
Christopher T. Walsh ◽  
Emil F. Pai ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Causative Agent ◽  
Crystallographic Analysis ◽  
Trypanothione Reductase

Antipicornavirus Compounds: Use of Rational Drug Design and Molecular Modelling

1993 ◽  
Vol 4 (1) ◽  
pp. 1-10 ◽  
Author(s):  
G. D. Diana ◽  
T. J. Nitz ◽  
J. P. Mallamo ◽  
A. Treasurywala
Keyword(s):  
Drug Design ◽  
Binding Site ◽  
Rational Drug Design ◽  
Human Rhinovirus ◽  
Dimensional Structure ◽  
X Ray ◽  
3 Dimensional ◽  
Rational Drug ◽  
Related Compounds ◽  
Maximum Occupancy

The discovery of antipicornavirus activity associated with disoxaril 1 and related compounds, and the elucidation of the 3-dimensional structure of human rhinovirus-14 and −1A has lead to the use of rational drug design in the search for more potent and broad spectrum agents. The use of volume maps based on the X-ray conformation of these compounds in human rhinovirus-14 has revealed space filling requirements for activity for this serotype which has been confirmed by the use of the programme CoMFA. The principle interactions of the compounds within the binding site appear hydrophobic in nature. These studies have shown that maximum occupancy of the binding site is associated with good antiviral activity.

Three-Dimensional Reconstruction Using Stereo Pairs from Serial Thick Sections

1977 ◽  
Vol 35 ◽  
pp. 562-563
Author(s):  
Robert Glaeser ◽  
Thomas Bauer ◽  
David Grano
Keyword(s):  
Three Dimensional ◽  
Dimensional Structure ◽  
Serial Sections ◽  
Thin Sections ◽  
3 Dimensional ◽  
Transmission Electron ◽  
Freeze Dried ◽  
Dimensional Reconstruction ◽  
Stereo Imagery ◽  
Whole Mounts

In transmission electron microscopy, the 3-dimensional structure of an object is usually obtained in one of two ways. For objects which can be included in one specimen, as for example with elements included in freeze- dried whole mounts and examined with a high voltage microscope, stereo pairs can be obtained which exhibit the 3-D structure of the element. For objects which can not be included in one specimen, the 3-D shape is obtained by reconstruction from serial sections. However, without stereo imagery, only detail which remains constant within the thickness of the section can be used in the reconstruction; consequently, the choice is between a low resolution reconstruction using a few thick sections and a better resolution reconstruction using many thin sections, generally a tedious chore. This paper describes an approach to 3-D reconstruction which uses stereo images of serial thick sections to reconstruct an object including detail which changes within the depth of an individual thick section.

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