The SCP2-thiolase-like protein (SLP) of Trypanosoma brucei is an enzyme involved in lipid metabolism.
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 Cβ2-Cα2 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 Å resolution) confirms that TbSLP has the canonical dimeric thiolase fold. In addition, the structures of the TbSLP-acetoacetyl-CoA (1.90 Å) and TbSLP-malonyl-CoA (2.30 Å) complexes reveal that the two oxyanion holes of the thiolase active site are preserved. TbSLP binds malonyl-CoA tightly (Kd 90 µM), acetoacetyl-CoA moderately (Kd 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. Proteins 2016; 84:1075-1096. © 2016 Wiley Periodicals, Inc.
Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, FIN-90014, Finland.|Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, 10461, USA.
Rajesh K
RK
Harijan
Centre De Résonance Magnétique Des Systèmes Biologiques (RMSB), UMR5536, Université De Bordeaux, CNRS, 146 Rue Léo Saignat, Bordeaux, 33076, France.|Laboratoire De Microbiologie Fondamentale Et Pathogénicité (MFP), UMR5234, Université De Bordeaux, CNRS, 146 Rue Léo Saignat, Bordeaux, 33076, France.
Muriel
M
Mazet
Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, FIN-90014, Finland.
Tiila R
TR
Kiema
Laboratoire De Biogenèse Membranaire, UMR-5200, Université De Bordeaux, CNRS, Bâtiment A3 - 1er Étage, INRA Bordeaux Aquitaine BP81, 71 Avenue Edouard Bourlaux, Villenave D'Ornon Cedex, 33883, France.
Guillaume
G
Bouyssou
Karolinska Institutet, Department of Laboratory Medicine, Division of Clinical Chemistry, Karolinska University Hospital, Stockholm, SE 141 86, Sweden.
Stefan E H
SE
Alexson
Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, FIN-90014, Finland.
Ulrich
U
Bergmann
Laboratoire De Biogenèse Membranaire, UMR-5200, Université De Bordeaux, CNRS, Bâtiment A3 - 1er Étage, INRA Bordeaux Aquitaine BP81, 71 Avenue Edouard Bourlaux, Villenave D'Ornon Cedex, 33883, France.
Patrick
P
Moreau
Centre for Immunity, Infection and Evolution and Centre for Translational and Chemical Biology, School of Biological Sciences, the King's Buildings, University of Edinburgh, Charlotte Auerbach Road, Edinburgh, EH9 3FL, United Kingdom.
Paul A M
PA
Michels
Centre De Résonance Magnétique Des Systèmes Biologiques (RMSB), UMR5536, Université De Bordeaux, CNRS, 146 Rue Léo Saignat, Bordeaux, 33076, France.|Laboratoire De Microbiologie Fondamentale Et Pathogénicité (MFP), UMR5234, Université De Bordeaux, CNRS, 146 Rue Léo Saignat, Bordeaux, 33076, France.
Frédéric
F
Bringaud
Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, FIN-90014, Finland.
Rik K
RK
Wierenga
D000105:Acetyl Coenzyme A / Q000737:chemistry* / Q000378:metabolism; D000214:Acyl Coenzyme A / Q000737:chemistry* / Q000378:metabolism; D000217:Acyltransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D050356:Lipid Metabolism; D008314:Malonates / Q000737:chemistry* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000072417:Protein Domains; D017433:Protein Structure, Secondary; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014346:Trypanosoma brucei brucei / Q000737:chemistry / Q000201:enzymology*
D000214:Acyl Coenzyme A; D008314:Malonates; D024101:Mitochondrial Proteins; D015800:Protozoan Proteins; D011993:Recombinant Fusion Proteins; C485184:enhanced green fluorescent protein; C010667:acetoacetyl CoA; D049452:Green Fluorescent Proteins; D000105:Acetyl Coenzyme A; C030290:malonic acid; D000217:Acyltransferases
SCP2-thiolase; SCP2-thiolase-like protein; Trypanosoma brucei; crystal structure; gene knockout; malonyl-CoA decarboxylase; malonyl-CoA:ACP transacylase; mitochondrial lipid metabolism