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1bzl

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CRYSTAL STRUCTURE OF TRYPANOSOMA CRUZI TRYPANOTHIONE REDUCTASE IN COMPLEX WITH TRYPANOTHIONE, AND THE STRUCTURE-BASED DISCOVERY OF NEW NATURAL PRODUCT INHIBITORS

Structural highlights

1bzl is a 2 chain structure with sequence from Trypanosoma cruzi. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TYTR_TRYCR Trypanothione is the parasite analog of glutathione; this enzyme is the equivalent of glutathione reductase.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

BACKGROUND: Trypanothione reductase (TR) helps to maintain an intracellular reducing environment in trypanosomatids, a group of protozoan parasites that afflict humans and livestock in tropical areas. This protective function is achieved via reduction of polyamine-glutathione conjugates, in particular trypanothione. TR has been validated as a chemotherapeutic target by molecular genetics methods. To assist the development of new therapeutics, we have characterised the structure of TR from the pathogen Trypanosoma cruzi complexed with the substrate trypanothione and have used the structure to guide database searches and molecular modelling studies. RESULTS: The TR-trypanothione-disulfide structure has been determined to 2.4 A resolution. The chemical interactions involved in enzyme recognition and binding of substrate can be inferred from this structure. Comparisons with the related mammalian enzyme, glutathione reductase, explain why each enzyme is so specific for its own substrate. A CH***O hydrogen bond can occur between the active-site histidine and a carbonyl of the substrate. This interaction contributes to enzyme specificity and mechanism by producing an electronic induced fit when substrate binds. Database searches and molecular modelling using the substrate as a template and the active site as receptor have identified a class of cyclic-polyamine natural products that are novel TR inhibitors. CONCLUSIONS: The structure of the TR-trypanothione enzyme-substrate complex provides details of a potentially valuable drug target. This information has helped to identify a new class of enzyme inhibitors as novel lead compounds worthy of further development in the search for improved medicines to treat a range of parasitic infections.

Crystal structure of Trypanosoma cruzi trypanothione reductase in complex with trypanothione, and the structure-based discovery of new natural product inhibitors.,Bond CS, Zhang Y, Berriman M, Cunningham ML, Fairlamb AH, Hunter WN Structure. 1999 Jan 15;7(1):81-9. PMID:10368274^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bond CS, Zhang Y, Berriman M, Cunningham ML, Fairlamb AH, Hunter WN. Crystal structure of Trypanosoma cruzi trypanothione reductase in complex with trypanothione, and the structure-based discovery of new natural product inhibitors. Structure. 1999 Jan 15;7(1):81-9. PMID:10368274

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1bzl"

@@ Line 3: / Line 3: @@
 <StructureSection load='1bzl' size='340' side='right'caption='[[1bzl]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1bzl]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BZL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BZL FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1bzl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_cruzi Trypanosoma cruzi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BZL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BZL FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GCG:BIS(GAMMA-GLUTAMYL-CYSTEINYL-GLYCINYL)SPERMIDINE'>GCG</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Trypanothione-disulfide_reductase Trypanothione-disulfide reductase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.1.12 1.8.1.12] </span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GCG:BIS(GAMMA-GLUTAMYL-CYSTEINYL-GLYCINYL)SPERMIDINE'>GCG</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1bzl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bzl OCA], [https://pdbe.org/1bzl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1bzl RCSB], [https://www.ebi.ac.uk/pdbsum/1bzl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1bzl ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/TYTR_TRYCR TYTR_TRYCR] Trypanothione is the parasite analog of glutathione; this enzyme is the equivalent of glutathione reductase.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 35: / Line 37: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Trypanothione-disulfide reductase]]
+[[Category: Trypanosoma cruzi]]
-[[Category: Berriman, M]]
+[[Category: Berriman M]]
-[[Category: Bond, C S]]
+[[Category: Bond CS]]
-[[Category: Cunningham, M]]
+[[Category: Cunningham M]]
-[[Category: Fairlamb, A H]]
+[[Category: Fairlamb AH]]
-[[Category: Hunter, W N]]
+[[Category: Hunter WN]]
-[[Category: Zhang, Y]]
+[[Category: Zhang Y]]
-[[Category: Fad dependent disulphide oxidoreductase]]
-[[Category: Oxidoreductase]]
-[[Category: Trypanothione reductase]]

1bzl

From Proteopedia

Current revision

CRYSTAL STRUCTURE OF TRYPANOSOMA CRUZI TRYPANOTHIONE REDUCTASE IN COMPLEX WITH TRYPANOTHIONE, AND THE STRUCTURE-BASED DISCOVERY OF NEW NATURAL PRODUCT INHIBITORS

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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