HARIJAN, Rajesh K.; MAZET, Muriel; KIEMA, Tiila R.; BOUYSSOU, Guillaume; ALEXSON, Stefan E. H.; BERGMANN, Ulrich; MOREAU, Patrick; MICHELS, Paul A. M.; BRINGAUD, Frederic; WIERENGA, Rik K.

doi:10.1002/prot.25054

MAZET, Muriel
Microbiologie Fondamentale et Pathogénicité [MFP]

KIEMA, Tiila R.

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Article de revue

Ce document a été publié dans

2016, vol. 84, n° 8, p. 1075-1096

Résumé en anglais

Bioinformatics studies have shown that the genomes of trypanosomatid species each encode one SCP2-thiolase-like protein (SLP), which is characterized by having the YDCF thiolase sequence fingerprint of the C beta 2-C alpha 2 loop. SLPs are only encoded by the genomes of these parasitic protists and not by those of mammals, including human. Deletion of the Trypanosoma brucei SLP gene (TbSLP) increases the doubling time of procyclic T. brucei and causes a 5-fold reduction of de novo sterol biosynthesis from glucose-and acetate-derived acetyl-CoA. Fluorescence analyses of EGFP-tagged TbSLP expressed in the parasite located the TbSLP in the mitochondrion. The crystal structure of TbSLP (refined at 1.75 angstrom resolution) confirms that TbSLP has the canonical dimeric thiolase fold. In addition, the structures of the TbSLP-acetoacetyl-CoA (1.90 angstrom) and TbSLP-malonyl-CoA (2.30 angstrom) complexes reveal that the two oxyanion holes of the thiolase active site are preserved. TbSLP binds malonyl-CoA tightly (K-d 90 mu M), acetoacetyl-CoA moderately (K-d 0.9 mM) and acetyl-CoA and CoA very weakly. TbSLP possesses low malonyl-CoA decarboxylase activity. Altogether, the data show that TbSLP is a mitochondrial enzyme involved in lipid metabolism.< Réduire

Mots clés en anglais

crystal structure

mitochondrial lipid metabolism

gene knockout

malonyl-CoA:ACP transacylase

malonyl-CoA decarboxylase

SCP2-thiolase-like protein

SCP2-thiolase

Trypanosoma brucei

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https://oskar-bordeaux.fr/handle/20.500.12278/183315

DOI

http://dx.doi.org/10.1002/prot.25054

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The SCP2-thiolase-like protein (SLP) of Trypanosoma brucei is an enzyme involved in lipid metabolism

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The SCP2-thiolase-like protein (SLP) of Trypanosoma brucei is an enzyme involved in lipid metabolism

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Résumé en anglais

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