The Crystal Structure of a Plant 3-Ketoacyl-CoA Thiolase Reveals the Potential for Redox Control of Peroxisomal Fatty Acid β-Oxidation

Ramasubramanian Sundaramoorthy, Elena Micossi, Magnus S. Alphey, Véronique Germain, James H. Bryce, Steve M. Smith, Gordon A. Leonard, William N. Hunter

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    Abstract

    Crystal structures of peroxisomal Arabidopsis thaliana 3-ketoacyl-CoA thiolase (AtKAT), an enzyme of fatty acid ß-oxidation, are reported. The subunit, a typical thiolase, is a combination of two similar a/ß domains capped with a loop domain. The comparison of AtKAT with the Saccharomyces cerevisiae homologue (ScKAT) structure reveals a different placement of subunits within the functional dimers and that a polypeptide segment forming an extended loop around the open catalytic pocket of ScKAT converts to a-helix in AtKAT, and occludes the active site. A disulfide is formed between Cys192, on this helix, and Cys138, a catalytic residue. Access to Cys138 is determined by the structure of this polypeptide segment. AtKAT represents an oxidized, previously unknown inactive form, whilst ScKAT is the reduced and active enzyme. A high level of sequence conservation is observed, including Cys192, in eukaryotic peroxisomal, but not mitochondrial or prokaryotic KAT sequences, for this labile loop/helix segment. This indicates that KAT activity in peroxisomes is influenced by a disulfide/dithiol change linking fatty acid ß-oxidation with redox regulation. © 2006 Elsevier Ltd. All rights reserved.

    Original languageEnglish
    Pages (from-to)347-357
    Number of pages11
    JournalJournal of Molecular Biology
    Volume359
    Issue number2
    DOIs
    Publication statusPublished - 2 Jun 2006

    Keywords

    • β-oxidation
    • 3-ketoacyl-CoA thiolase
    • Arabidopsis thaliana
    • redox regulation
    • Saccharomyces cerevisiae

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    Sundaramoorthy, R., Micossi, E., Alphey, M. S., Germain, V., Bryce, J. H., Smith, S. M., Leonard, G. A., & Hunter, W. N. (2006). The Crystal Structure of a Plant 3-Ketoacyl-CoA Thiolase Reveals the Potential for Redox Control of Peroxisomal Fatty Acid β-Oxidation. Journal of Molecular Biology, 359(2), 347-357. https://doi.org/10.1016/j.jmb.2006.03.032