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Non-covalent complex of and DAHP synthase and chorismate mutase from Corynebacterium glutamicum with bound transition state analogNon-covalent complex of and DAHP synthase and chorismate mutase from Corynebacterium glutamicum with bound transition state analog
Structural highlights
FunctionPublication Abstract from PubMedCorynebacterium glutamicum is widely used for the industrial production of amino acids, nucleotides, and vitamins. The shikimate pathway enzymes DAHP synthase (CgDS; Cg2391) and chorismate mutase (CgCM; Cgl0853) play a key role for the biosynthesis of aromatic compounds. Here we show that CgCM requires the formation of a complex with CgDS to achieve full activity, and that both CgCM and CgDS are feedback regulated by aromatic amino acids binding to CgDS. Kinetic analysis showed that Phe and Tyr inhibit CgCM activity by inter-enzyme allostery, whereas Trp binding to CgDS strongly activates CgCM. Mechanistic insights were gained from crystal structures of the CgCM homodimer, tetrameric CgDS, and the heterooctameric CgCM-CgDS complex, refined to 1.1, 2.5, and 2.2 A resolution, respectively. Structural details from the allosteric binding sites reveal that DAHP synthase is recruited as the dominant regulatory platform to control the shikimate pathway, similar to the corresponding enzyme complex from Mycobacterium tuberculosis. Inter-enzyme allosteric regulation of chorismate mutase in Corynebacterium glutamicum: Structural basis of feedback activation by Trp.,Burschowsky D, Thorbjornsrud HV, Heim JB, Fahrig-Kamarauskaite J, Wurth-Roderer K, Kast P, Krengel U Biochemistry. 2017 Nov 27. doi: 10.1021/acs.biochem.7b01018. PMID:29178787[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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