4f0x
From Proteopedia
Crystal structure of human Malonyl-CoA Decarboxylase (Peroxisomal Isoform)
Structural highlights
Disease[DCMC_HUMAN] Malonic aciduria. Defects in MLYCD are the cause of malonyl-CoA decarboxylase deficiency (MLYCD deficiency) [MIM:248360]. MLYCD deficiency is an autosomal recessive disease characterized by abdominal pain, chronic constipation, episodic vomiting, metabolic acidosis and malonic aciduria. Function[DCMC_HUMAN] Catalyzes the conversion of malonyl-CoA to acetyl-CoA. In the fatty acid biosynthesis MCD selectively removes malonyl-CoA and thus assures that methyl-malonyl-CoA is the only chain elongating substrate for fatty acid synthase and that fatty acids with multiple methyl side chains are produced. In peroxisomes it may be involved in degrading intraperoxisomal malonyl-CoA, which is generated by the peroxisomal beta-oxidation of odd chain-length dicarboxylic fatty acids. Publication Abstract from PubMedDecarboxylation of malonyl-CoA to acetyl-CoA by Malonyl-CoA Decarboxylase (EC 4.1.1.9) is an essential facet in the regulation of fatty acid metabolism. The structure of human peroxisomal Malonyl-CoA Decarboxylase reveals a molecular tetramer that is best described as a dimer of structural heterodimers, in which the two subunits present markedly different conformations. This molecular organization is consistent with half-of-the-sites reactivity. Each subunit has an all-helix N-terminal domain and a catalytic C-terminal domain with a histone acetyltransferase fold (GNAT superfamily). Inter-subunit disulphide bridges, Cys206-Cys206 and Cys243-Cys243, can link the four subunits of the tetramer imparting positive cooperativity to the catalytic process. Combination of a half-of-the-sites mechanism within each structural heterodimer and positive cooperativity in the tetramer produces a complex regulatory picture that is further complicated by the multiple intracellular locations of the enzyme. Transport into the peroxisome has been investigated by docking human Malonyl-CoA Decarboxylase to the peroxisomal import protein Peroxin 5, which revealed interactions that extend beyond the C-terminal targeting motif. Structural asymmetry and disulphide bridges among subunits modulate the activity of human Malonyl-CoA Decarboxylase.,Aparicio D, Perez R, Carpena X, Diaz M, Ferrer JC, Loewen PC, Fita I J Biol Chem. 2013 Mar 11. PMID:23482565[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Malonyl-CoA decarboxylase | Aparicio, D | Fita, I | Perez, R | Enzyme | Lyase | Peroxisome
