MF7000211 Chorismate mutase (Mycobacterium tuberculosis) 2vkl X-ray 1.65 Homodimer Mycobacterium tuberculosis 19556970 Sasso S, Okvist M, Roderer K, Gamper M, Codoni G, Krengel U, Kast P EMBO J. 2009 14 28 2128-42 Chorismate mutase catalyzes a key step in the shikimate biosynthetic pathway towards phenylalanine and tyrosine. Curiously, the intracellular chorismate mutase of Mycobacterium tuberculosis (MtCM; Rv0948c) has poor activity and lacks prominent active-site residues. However, its catalytic efficiency increases >100-fold on addition of DAHP synthase (MtDS; Rv2178c), another shikimate-pathway enzyme. The 2.35 A crystal structure of the MtCM-MtDS complex bound to a transition-state analogue shows a central core formed by four MtDS subunits sandwiched between two MtCM dimers. Structural comparisons imply catalytic activation to be a consequence of the repositioning of MtCM active-site residues on binding to MtDS. The mutagenesis of the C-terminal extrusion of MtCM establishes conserved residues as part of the activation machinery. The chorismate-mutase activity of the complex, but not of MtCM alone, is inhibited synergistically by phenylalanine and tyrosine. The complex formation thus endows the shikimate pathway of M. tuberculosis with an important regulatory feature. Experimental evidence suggests that such non-covalent enzyme complexes comprising an AroQ(delta) subclass chorismate mutase like MtCM are abundant in the bacterial order Actinomycetales. GO:0004106 chorismate mutase activity GO:0005737 cytoplasm GO:0005886 plasma membrane GO:0008652 amino acid biosynthetic process GO:0009095 aromatic amino acid family biosynthetic process, prephenate pathway GO:0046417 chorismate metabolic process GO:0009697 salicylic acid biosynthetic process 2 1 Homooligomeric enzymes Homodimeric enzymes All chains according to the most probable oligomerization state stored in PDBe were considered. A Intracellular chorismate mutase Mycobacterium tuberculosis P9WIC1 28 104 73% MRPEPPHHENAELAAMNLEMLESQPVPEIDTLREEIDRLDAEILALVKRRAEVSKAIGKARMASGGTRLVHSREMKVIERYSELGPDGKDLAILLLRLGRGRLGH 105 secondary structure helix 13 50 secondary structure helix 57 68 secondary structure helix 70 84 pfam PF01817 Chorismate mutase type II 32 88 A-2 Intracellular chorismate mutase Mycobacterium tuberculosis P9WIC1 28 104 73% MRPEPPHHENAELAAMNLEMLESQPVPEIDTLREEIDRLDAEILALVKRRAEVSKAIGKARMASGGTRLVHSREMKVIERYSELGPDGKDLAILLLRLGRGRLGH 105 pfam PF01817 Chorismate mutase type II 32 88 Indirect evidence The full structure participates in mutual synergistic folding. Chorismate mutase type II The enzyme is an intertwined dimer of three helices with connecting loops. The N-terminal helices of the two monomers twine together to form an anti-parallel coiled-coil with a hydrophobic interaction surface. The loop between the first and second helices is disordered (PMID:16914555). A N/A A-2 N/A MF7000162 MF7000212 MF7000163 MF7000211 MF7000164 MF7000165 MF7000209 MF7000210