Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/113865
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dc.contributor.authorMarshall, A.-
dc.contributor.authorBond, C.-
dc.contributor.authorBruning, J.-
dc.date.issued2018-
dc.identifier.citationACS Catalysis, 2018; 8(3):1973-1989-
dc.identifier.issn2155-5435-
dc.identifier.issn2155-5435-
dc.identifier.urihttp://hdl.handle.net/2440/113865-
dc.description.abstractCytosolic thiolase (CT) catalyzes the reversible Claisen condensation of two molecules of acetyl-CoA to produce acetoacetyl-CoA. The reaction cycle proceeds via a ping-pong mechanism involving an acetylated enzyme intermediate and two separate oxyanion holes which stabilize negatively charged reaction intermediates. This is the initial step in the synthesis of ergosterol in the prominent fungal pathogen Aspergillus fumigatus and is essential for the growth and survival of the organism. Here, we present crystal structures of A. fumigatus CT in liganded and apo forms and in a complex with different monovalent cations. Careful observation of the electron density at the active sites of two different afCT structures crystallized in the presence of acetyl-CoA shows that our crystals have trapped various stages of the thiolase catalytic cycle, including two tetrahedral reaction intermediates that have previously eluded structural characterization. Unexpectedly, we have also shown that afCT is activated by monovalent cations, a biochemical property previously thought to apply only to the mitochondrial biosynthetic thiolase, with a preference for potassium ions. Structures of fungal CT provide valuable insight into the thiolase reaction cycle and allosteric activation of members of this class of enzymes by monovalent cations.-
dc.description.statementofresponsibilityAndrew C. Marshall, Charles S. Bond, and John B. Bruning-
dc.language.isoen-
dc.publisherAmerican Chemical Society-
dc.rights© 2018 American Chemical Society-
dc.subjectBbiosynthetic thiolase; acetoacetyl-CoA; Claisen condensation; tetrahedral reaction intermediate; monovalent cation activation-
dc.titleStructure of Aspergillus fumigatus Cytosolic thiolase: trapped tetrahedral reaction intermediates and activation by monovalent cations-
dc.typeJournal article-
dc.identifier.doi10.1021/acscatal.7b02873-
pubs.publication-statusPublished-
dc.identifier.orcidMarshall, A. [0000-0002-9770-4594]-
dc.identifier.orcidBruning, J. [0000-0002-6919-1824]-
Appears in Collections:Aurora harvest 3
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