Linked Life Data

19523496

Source:http://linkedlifedata.com/resource/pubmed/id/19523496

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-8-24
pubmed:abstractText
The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease (American trypanosomiasis), a neglected disease of Central and South America. Polyamines are small organic cations that are required for cell growth and their biosynthesis has been the target of drug discovery efforts in both T. cruzi and the related Trypanosoma brucei parasites. Here we show that, as previously demonstrated for T. brucei, S-adenosylmethionine decarboxylase (AdoMetDC) from T. cruzi forms a heterodimer with prozyme, an inactive homolog that arose by gene duplication of the canonical enzyme uniquely in the trypanosomatids. The T. cruzi AdoMetDC/prozyme heterodimer is 110-fold more active than homodimeric AdoMetDC. Unlike for T. brucei AdoMetDC, the activity of the T. cruzi heterodimer is further stimulated by putrescine to generate an enzyme with similar catalytic efficiency to the fully activated T. brucei enzyme. The effects of prozyme on T. cruzi AdoMetDC are mediated by an increase in k(cat), while the predominant effect of putrescine is to lower the K(m). Finally we demonstrate that the cross-species heterodimers of T. cruzi and T. brucei AdoMetDC and prozyme pairs are functional, and that putrescine is required for prozyme to fully activate the mixed species heterodimers. These data demonstrate that prozyme mediated activation of AdoMetDC is a common mechanism required to regulate AdoMetDC activity in the trypanosomatids.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1872-9428
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
168
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1-6
pubmed:dateRevised
2010-12-3
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Cross-species activation of trypanosome S-adenosylmethionine decarboxylase by the regulatory subunit prozyme.
pubmed:affiliation
Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park Road, Dallas, TX 75390-9041, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural