IntroductionThe SCP2-thiolase is a member of the thiolase family of enzymes[1]. It has low sequence identity with any of the other thiolases. Like many other thiolases it is a dimer in solution. In the 6HSP crystal structure there are two monomers per asymmetric unit. One monomer forms the classical dimer with a two-fold related symmetry mate. The other monomer has a different packing and it is not forming the classical dimer: its structure is the structure of the monomer. There are large structural differences between these two monomers. The comparison of the structures of the "dimerised" monomer and the single monomer visualises the structural changes that happen when the single monomer dimerises to form the mature dimer. The A-monomer is the single monomer, and the B-monomer is forming a dimer with its two-fold crystallographically related symmetry copy. Each subunit can be divided in a color coded N-terminal domain, a loop domain and a C-terminal domain. The active site is at the dimer interface. Four loops provide critically important catalytic residues. These loops have characteristic sequence fingerprints [1]. These four loops are residues 87-89 (Nβ3-Nα3), 298-301 (Cβ2-Cα2), 347-349 (Cβ3-Cα3), 385-387 (Cβ4-Cβ5). Function and DiseaseThe SCP2 thiolase functions in the bile acid synthesis pathway [2]. SCP2-thiolase is synthesised as a larger protein, having the thiolase part and at the C-terminal end there is an extra domainn, the SCP2-domain. This domain has the sequence SKL at its C-terminus, which functions as the peroxisomal targetting sequence. In the peroxisome the SCP2-domain is proteolytically cleaved off, and the SCP2-thiolase chain is found to be present in the peroxisome, as described by Wanders and coworkers, who also described the deficiency symptoms in case the SCP2-thiolase is not properly expressed. [3] Structural highlightsWhen the A and B monomers are compared the structural differences can best be seen in this morph.
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This page was last modified 08:44, 19 January 2020.