The crystal structure of a Plant 3-ketoacyl-CoA thiolase reveals the potential for redox control of peroxisomal fatty acid bβ-oxidation

R. Sundaramoorthy, E. Micossi, M.S. Alphey, V. Germain, J.H. Bryce, Steven Smith, G.A. Leonard, W.N. Hunter

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Crystal structures of peroxisomal Arabidopsis thaliana 3-ketoacyl-CoA thiolase (AtKAT), an enzyme of fatty acid β-oxidation, are reported. The subunit, a typical thiolase, is a combination of two similar α/β 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 α-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 β-oxidation with redox regulation.
Original languageEnglish
Pages (from-to)347-57
JournalJournal of Molecular Biology
Volume359
Issue number2
DOIs
Publication statusPublished - 2006

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