English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Crystal structure of the Trypanosoma cruzi trypanothione reductase-mepacrine complex

Jacoby, E. M., Schlichting, I., Lantwin, C. B., Kabsch, W., & Krauth-Siegel, R. L. (1996). Crystal structure of the Trypanosoma cruzi trypanothione reductase-mepacrine complex. Proteins: Structure, Function, and Genetics, 24(1), 73-80. doi:10.1002/(SICI)1097-0134(199601)24:1<73:AID-PROT5>3.0.CO;2-P.

Item is

Basic

show hide
Genre: Journal Article
Alternative Title : Crystal structure of the Trypanosoma cruzi trypanothione reductase-mepacrine complex

Files

show Files
hide Files
:
ProtStructFunctBioinformat_24_1996_73.pdf (Any fulltext), 801KB
 
File Permalink:
-
Name:
ProtStructFunctBioinformat_24_1996_73.pdf
Description:
-
Visibility:
Restricted (Max Planck Institute for Medical Research, MHMF; )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Creators

show
hide
 Creators:
Jacoby, Elke M., Author
Schlichting, Ilme1, Author              
Lantwin, Christina B., Author
Kabsch, Wolfgang1, 2, Author              
Krauth-Siegel, R. Luise, Author
Affiliations:
1Emeritus Group Biophysics, Max Planck Institute for Medical Research, Max Planck Society, ou_1497712              
2Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Max Planck Society, ou_1497700              

Content

show
hide
Free keywords: -
 Abstract: The three-dimensional structure of the complex between Trypanosoma cruzi trypanothione reductase (TR) (EC 1.6.4.8) and the antiparasitic drug mepacrine (quinacrine) has been solved at 2.9 angstoms resolution. Mepacrine is a competitive inhibitor of TR but does not affect human glutathione reductase (GR), a closely related host enzyme. Of particular importance for inhibitor binding are four amino acid residues in the disulfide substrate-binding site of TR that are not conserved in human GR, namely, Glu-18 (Ala-34 in GR), Trp-21 (Arg-37), Ser-109 (Ile-113), and Met-113 (Asn-117). The acridine ring of mepacrine is fixed at the active site close to the hydrophobic wall formed by Trp-21 and Met-113. Specific pairwise interactions between functional groups of the drug and amino acid side chains include the ring nitrogen and Met-113, the chlorine atom and Trp-21, and the oxymethyl group and Ser-109. The alkylamino chain of mepacrine points into the inner region of the active site and is held in position by a solvent-mediated hydrogen bond to Glu-18. The structure of the complex shows for the first time the atomic interactions between TR and an inhibitory ligand. This is a crucial step towards the rational design of inhibitors that might be suited as drugs against Chagas disease

Details

show
hide
Language(s): eng - English
 Dates: 1995-05-191995-08-141996-01
 Publication Status: Published in print
 Pages: 8
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Proteins: Structure, Function, and Genetics
  Other : Proteins: Struct., Funct., Genet.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: New York, NY : John Wiley & Sons
Pages: - Volume / Issue: 24 (1) Sequence Number: - Start / End Page: 73 - 80 Identifier: ISSN: 0887-3585
CoNE: https://pure.mpg.de/cone/journals/resource/954925553393