Circular permutation of 5-aminolevulinate synthase as a tool to evaluate folding, structure and function.
5-Aminolevulinate synthase, a pyridoxal 5'-phosphate-dependent enzyme, catalyzes the condensation of glycine with succinyl-coenzyme A to yield aminolevulinate, carbon dioxide and CoA. This reaction corresponds to the first and regulatory step of the mammalian heme biosynthetic pathway. Mutations in the erythroid aminolevulinate synthase gene are associated with X-linked sideroblastic anemia, an erythropoietic disorder characterized by the presence of hypochromic-microcytic erythrocytes in peripheral blood and ring sideroblasts in bone marrow. In the past five years, transient kinetic studies in conjunction with three-dimensional structure models and engineered variants of aminolevulinate synthase have been instrumental in understanding the individual steps of the catalytic mechanism of aminolevulinate synthase. The mechanism of folding, assembly of the two subunits into a functional, dimeric holoenzyme has been recently explored in this laboratory using circular permutation of aminolevulinate synthase.
Ferreira
Gloria C
GC
Department of Biochemistry and Molecular Biology, College of Medicine, University of South Florida, Tampa 33612, USA. gferreir@hsc.med.usf.edu
Cheltsov
Anton V
AV
D000624:5-Aminolevulinate Synthetase / Q000737:chemistry*; D000818:Animals; D006801:Humans; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry; D017510:Protein Folding; D013329:Structure-Activity Relationship
D010446:Peptide Fragments; D000624:5-Aminolevulinate Synthetase