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

Journal of Molecular Biology
Ramasubramanian SundaramoorthyWilliam N Hunter

Abstract

Crystal structures of peroxisomal Arabidopsis thaliana 3-ketoacyl-CoA thiolase (AtKAT), an enzyme of fatty acid beta-oxidation, are reported. The subunit, a typical thiolase, is a combination of two similar alpha/beta 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 alpha-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 beta-oxidation with redox regulation.

References

Mar 1, 1991·Acta Crystallographica. Section A, Foundations of Crystallography·T A JonesM Kjeldgaard
Oct 25, 1994·Proceedings of the National Academy of Sciences of the United States of America·J R GloverR A Rachubinski
Apr 1, 1993·Plant Molecular Biology·R Preisig-Müller, H Kindl
Mar 25, 1999·Acta Crystallographica. Section D, Biological Crystallography·D W Cruickshank
Apr 13, 2000·Biochimica Et Biophysica Acta·J K Hiltunen, Y Qin
Jan 3, 2001·Acta Crystallographica. Section D, Biological Crystallography·M D WinnG N Murshudov
Nov 15, 2002·Natural Product Reports·Richard J Heath, Charles O Rock
Dec 31, 2002·Current Opinion in Structural Biology·Jung-Ja P Kim, Kevin P Battaile
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Sep 9, 2005·The Plant Journal : for Cell and Molecular Biology·Helen Pinfield-WellsIan A Graham

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Citations

May 14, 2010·The Journal of Biological Chemistry·Valerie E PyeAnette Henriksen
May 1, 2008·Annual Review of Plant Biology·Ian A Graham
Dec 17, 2009·International Journal of Biological Sciences·James H DyerAnke C Schiedel
Dec 30, 2014·Redox Biology·Xiaofeng WangChangle Ma
Sep 24, 2015·Nature Communications·Sangwoo KimKyung-Jin Kim
Aug 2, 2013·The Journal of Biological Chemistry·Changle MaSuresh Subramani

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