Crystal structure of protoporphyrinogen oxidase from Myxococcus xanthus and its complex with the inhibitor acifluorfen

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dc.contributor.authorCorradi, Hazel R
dc.contributor.authorCorrigall, Anne V
dc.contributor.authorBoix, Ester
dc.contributor.authorMohan, C Gopi
dc.contributor.authorSturrock, Edward D
dc.contributor.authorMeissner, Peter N
dc.contributor.authorAcharya, K Ravi
dc.date.accessioned2016-09-05T19:14:06Z
dc.date.available2016-09-05T19:14:06Z
dc.date.issued2006
dc.date.updated2016-09-02T19:11:45Z
dc.description.abstractProtoporphyrinogen IX oxidase, a monotopic membrane protein, which catalyzes the oxidation of protoporphyrinogen IX to protoporphyrin IX in the heme/chlorophyll biosynthetic pathway, is distributed widely throughout nature. Here we present the structure of protoporphyrinogen IX oxidase from Myxococcus xanthus, an enzyme with similar catalytic properties to human protoporphyrinogen IX oxidase that also binds the common plant herbicide, acifluorfen. In the native structure, the planar porphyrinogen substrate is mimicked by a Tween 20 molecule, tracing three sides of the macrocycle. In contrast, acifluorfen does not mimic the planarity of the substrate but is accommodated by the shape of the binding pocket and held in place by electrostatic and aromatic interactions. A hydrophobic patch surrounded by positively charged residues suggests the position of the membrane anchor, differing from the one proposed for the tobacco mitochondrial protoporphyrinogen oxidase. Interestingly, there is a discrepancy between the dimerization state of the protein in solution and in the crystal. Conserved structural features are discussed in relation to a number of South African variegate porphyria-causing mutations in the human enzyme.en_ZA
dc.identifierhttp://dx.doi.org/10.1074/jbc.M606640200
dc.identifier.apacitationCorradi, H. R., Corrigall, A. V., Boix, E., Mohan, C. G., Sturrock, E. D., Meissner, P. N., & Acharya, K. R. (2006). Crystal structure of protoporphyrinogen oxidase from Myxococcus xanthus and its complex with the inhibitor acifluorfen. <i>Journal of Biological Chemistry</i>, http://hdl.handle.net/11427/21677en_ZA
dc.identifier.chicagocitationCorradi, Hazel R, Anne V Corrigall, Ester Boix, C Gopi Mohan, Edward D Sturrock, Peter N Meissner, and K Ravi Acharya "Crystal structure of protoporphyrinogen oxidase from Myxococcus xanthus and its complex with the inhibitor acifluorfen." <i>Journal of Biological Chemistry</i> (2006) http://hdl.handle.net/11427/21677en_ZA
dc.identifier.citationCorradi, Hazel R., Anne V. Corrigall, Ester Boix, C. Gopi Mohan, Edward D. Sturrock, Peter N. Meissner, and K. Ravi Acharya. "Crystal structure of protoporphyrinogen oxidase from Myxococcus xanthus and its complex with the inhibitor acifluorfen." Journal of Biological Chemistry 281, no. 50 (2006): 38625-38633.en_ZA
dc.identifier.issn0021-9258en_ZA
dc.identifier.ris TY - Journal Article AU - Corradi, Hazel R AU - Corrigall, Anne V AU - Boix, Ester AU - Mohan, C Gopi AU - Sturrock, Edward D AU - Meissner, Peter N AU - Acharya, K Ravi AB - Protoporphyrinogen IX oxidase, a monotopic membrane protein, which catalyzes the oxidation of protoporphyrinogen IX to protoporphyrin IX in the heme/chlorophyll biosynthetic pathway, is distributed widely throughout nature. Here we present the structure of protoporphyrinogen IX oxidase from Myxococcus xanthus, an enzyme with similar catalytic properties to human protoporphyrinogen IX oxidase that also binds the common plant herbicide, acifluorfen. In the native structure, the planar porphyrinogen substrate is mimicked by a Tween 20 molecule, tracing three sides of the macrocycle. In contrast, acifluorfen does not mimic the planarity of the substrate but is accommodated by the shape of the binding pocket and held in place by electrostatic and aromatic interactions. A hydrophobic patch surrounded by positively charged residues suggests the position of the membrane anchor, differing from the one proposed for the tobacco mitochondrial protoporphyrinogen oxidase. Interestingly, there is a discrepancy between the dimerization state of the protein in solution and in the crystal. Conserved structural features are discussed in relation to a number of South African variegate porphyria-causing mutations in the human enzyme. DA - 2006 DB - OpenUCT DP - University of Cape Town J1 - Journal of Biological Chemistry LK - https://open.uct.ac.za PB - University of Cape Town PY - 2006 SM - 0021-9258 T1 - Crystal structure of protoporphyrinogen oxidase from Myxococcus xanthus and its complex with the inhibitor acifluorfen TI - Crystal structure of protoporphyrinogen oxidase from Myxococcus xanthus and its complex with the inhibitor acifluorfen UR - http://hdl.handle.net/11427/21677 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/21677
dc.identifier.vancouvercitationCorradi HR, Corrigall AV, Boix E, Mohan CG, Sturrock ED, Meissner PN, et al. Crystal structure of protoporphyrinogen oxidase from Myxococcus xanthus and its complex with the inhibitor acifluorfen. Journal of Biological Chemistry. 2006; http://hdl.handle.net/11427/21677.en_ZA
dc.languageengen_ZA
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.sourceJournal of Biological Chemistryen_ZA
dc.source.urihttp://www.asbmb.org/page.aspx?id=598
dc.titleCrystal structure of protoporphyrinogen oxidase from Myxococcus xanthus and its complex with the inhibitor acifluorfenen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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