1TYP

SUBSTRATE INTERACTIONS BETWEEN TRYPANOTHIONE REDUCTASE AND N1-GLUTATHIONYLSPERMIDINE DISULPHIDE AT 0.28-NM RESOLUTION

Summary for 1TYP

• Entry DOI: 10.2210/pdb1typ/pdb
• Descriptor: TRYPANOTHIONE REDUCTASE, FLAVIN-ADENINE DINUCLEOTIDE, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (6 entities in total)
• Functional Keywords: oxidoreductase
• Biological source: Crithidia fasciculata
• Cellular location: Cytoplasm: P39040
• Total number of polymer chains: 2
• Total formula weight: 110671.80

Authors

Bailey, S.,Hunter, W.N. (deposition date: 1992-06-29, release date: 1994-01-31, Last modification date: 2024-06-05)

Primary citation

Bailey, S.,Smith, K.,Fairlamb, A.H.,Hunter, W.N.
Substrate interactions between trypanothione reductase and N1-glutathionylspermidine disulphide at 0.28-nm resolution.
Eur.J.Biochem., 213:67-75, 1993

PubMed Abstract: The enzyme trypanothione reductase has been identified as a prime target for the rational design of inhibitors which may have clinical use in the treatment of tropical diseases caused by the genera Trypanosoma and Leishmania. To aid the design or identification of new inhibitors of this enzyme we have elucidated the structural detail of a trypanothione reductase complexed with one of the naturally occurring substrates, N1-glutathionylspermidine disulphide, by single-crystal X-ray diffraction methods at 0.28-nm resolution. The model for the Crithidia fasciculata enzyme-substrate complex has an R-factor of 14.8% and root-mean-square deviations of 0.0015 nm and 3.3 degrees on bond lengths and angles respectively. Hydrogen bonding and van der Waals interactions between the enzyme and substrate are dominated by the amino acid side chains. The substrate binds in a rigid active site such that one glutathione moiety is in a V-shape, the other in an extended conformation. One spermidine moiety binds closely to a hydrophobic patch in the active site formed by a tryptophan and a methionine. Distances between the methionine S delta and the terminal N of this spermidine suggest that a hydrogen bond may supplement the hydrophobic interactions in this part of the active site.

PubMed: 8477734
DOI: 10.1111/j.1432-1033.1993.tb17734.x

Experimental method

X-RAY DIFFRACTION (2.8 Å)