2vkl
X-ray crystal structure of the intracellular Chorismate mutase from Mycobactrerium Tuberculosis in complex with malate
Structural highlights
FunctionCHMU_MYCTU Catalyzes the Claisen rearrangement of chorismate to prephenate. Probably involved in the aromatic amino acid biosynthesis.[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedChorismate 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. Structure and function of a complex between chorismate mutase and DAHP synthase: efficiency boost for the junior partner.,Sasso S, Okvist M, Roderer K, Gamper M, Codoni G, Krengel U, Kast P EMBO J. 2009 Jul 22;28(14):2128-42. Epub 2009 Jun 25. PMID:19556970[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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