SwePub
Sök i LIBRIS databas

  Utökad sökning

WFRF:(Gibson K.)
 

Sökning: WFRF:(Gibson K.) > (2000-2004) > Arginase plays a pi...

Arginase plays a pivotal role in polyamine precursor metabolism in Leishmania. Characterization of gene deletion mutants.

Roberts, Sigrid C (författare)
Tancer, Michael J (författare)
Polinsky, Michelle R (författare)
visa fler...
Gibson, K Michael (författare)
Heby, Olle (författare)
Umeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet)
Ullman, Buddy (författare)
Heby
visa färre...
 (creator_code:org_t)
2004
2004
Engelska.
Ingår i: J Biol Chem. - 0021-9258. ; 279:22, s. 23668-78
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • The polyamine pathway of protozoan parasites has been successfully targeted in anti-parasitic therapies and is significantly different from that of the mammalian host. To gain knowledge into the metabolic routes by which parasites synthesize polyamines and their precursors, the arginase gene was cloned from Leishmania mexicana, and Deltaarg null mutants were created by double targeted gene replacement and characterized. The ARG sequence exhibited significant homology to ARG proteins from other organisms and predicted a peroxisomal targeting signal (PTS-1) that steers proteins to the glycosome, an organelle unique to Leishmania and related parasites. ARG was subsequently demonstrated to be present in the glycosome, whereas the polyamine biosynthetic enzymes, in contrast, were shown to be cytosolic. The Deltaarg knockouts expressed no ARG activity, lacked an intracellular ornithine pool, and were auxotrophic for ornithine or polyamines. The ability of the Deltaarg null mutants to proliferate could be restored by pharmacological supplementation, either with low putrescine or high ornithine or spermidine concentrations, or by complementation with an arginase episome. Transfection of an arg construct lacking the PTS-1 directed the synthesis of an arg that mislocalized to the cytosol and notably also complemented the genetic lesion and restored polyamine prototrophy to the Deltaarg parasites. This molecular, biochemical, and genetic dissection of ARG function in L. mexicana promastigotes establishes: (i) that the enzyme is essential for parasite viability; (ii) that Leishmania, unlike mammalian cells, expresses only one ARG activity; (iii) that the sole vital function of ARG is to provide polyamine precursors for the parasite; and (iv) that ARG is present in the glycosome, but this subcellular milieu is not essential for its role in polyamine biosynthesis.

Nyckelord

Amino Acid Sequence
Animals
Arginase/genetics/*metabolism
Cloning; Molecular
Gene Deletion
Leishmania/*enzymology/genetics/growth & development
Molecular Sequence Data
Phylogeny
Polyamines/metabolism
Sequence Alignment

Publikations- och innehållstyp

ref (ämneskategori)
art (ämneskategori)

Hitta via bibliotek

Till lärosätets databas

Sök utanför SwePub

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy