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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2008-8-22
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pubmed:databankReference |
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pubmed:abstractText |
TbTDPX (Trypanosoma brucei tryparedoxin-dependent peroxidase) is a genetically validated drug target in the fight against African sleeping sickness. Despite its similarity to members of the GPX (glutathione peroxidase) family, TbTDPX2 is functional as a monomer, lacks a selenocysteine residue and relies instead on peroxidatic and resolving cysteine residues for catalysis and uses tryparedoxin rather than glutathione as electron donor. Kinetic studies indicate a saturable Ping Pong mechanism, unlike selenium-dependent GPXs, which display infinite K(m) and V(max) values. The structure of the reduced enzyme at 2.1 A (0.21 nm) resolution reveals that the catalytic thiol groups are widely separated [19 A (0.19 nm)] and thus unable to form a disulphide bond without a large conformational change in the secondary-structure architecture, as reported for certain plant GPXs. A model of the oxidized enzyme structure is presented and the implications for small-molecule inhibition are discussed.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18522537-10672177,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18522537-11517324,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18522537-11842085,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18522537-12466271,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18522537-12791697,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18522537-12824332,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18522537-14580959,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18522537-15110394,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18522537-15215472,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18522537-15299374,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18522537-15299926,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18522537-15558583,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18522537-15572765,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18522537-15664987,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18522537-16008527,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18522537-17040206,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18522537-17456049,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18522537-17531267,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18522537-17630701,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18522537-17922848,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18522537-18382742,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18522537-3990705,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18522537-6852035,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18522537-7788290,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18522537-8590014,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18522537-8662544
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1470-8728
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
414
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
375-81
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:18522537-Amino Acid Sequence,
pubmed-meshheading:18522537-Animals,
pubmed-meshheading:18522537-Binding Sites,
pubmed-meshheading:18522537-Crystallography, X-Ray,
pubmed-meshheading:18522537-Cytosol,
pubmed-meshheading:18522537-Kinetics,
pubmed-meshheading:18522537-Mitochondria,
pubmed-meshheading:18522537-Models, Molecular,
pubmed-meshheading:18522537-Molecular Sequence Data,
pubmed-meshheading:18522537-Peroxidases,
pubmed-meshheading:18522537-Protozoan Proteins,
pubmed-meshheading:18522537-Recombinant Proteins,
pubmed-meshheading:18522537-Sequence Alignment,
pubmed-meshheading:18522537-Trypanosoma brucei brucei
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pubmed:year |
2008
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pubmed:articleTitle |
Structural and mechanistic insights into type II trypanosomatid tryparedoxin-dependent peroxidases.
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pubmed:affiliation |
Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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