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dc.contributor.authorBustad, Helene J.
dc.contributor.authorKallio, Juha Pekka
dc.contributor.authorLaitaoja, Mikko
dc.contributor.authorToska, Karen
dc.contributor.authorKursula, Inari
dc.contributor.authorMartinez, Aurora
dc.contributor.authorJänis, Janne
dc.date.accessioned2021-08-12T08:05:05Z
dc.date.available2021-08-12T08:05:05Z
dc.date.created2021-06-16T12:58:30Z
dc.date.issued2021
dc.identifier.issn2589-0042
dc.identifier.urihttps://hdl.handle.net/11250/2767459
dc.description.abstractPorphobilinogen deaminase (PBGD), the third enzyme in the heme biosynthesis, catalyzes the sequential coupling of four porphobilinogen (PBG) molecules into a heme precursor. Mutations in PBGD are associated with acute intermittent porphyria (AIP), a rare metabolic disorder. We used Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) to demonstrate that wild-type PBGD and AIP-associated mutant R167W both existed as holoenzymes (Eholo) covalently attached to the dipyrromethane cofactor, and three intermediate complexes, ES, ES2, and ES3, where S represents PBG. In contrast, only ES2 was detected in AIP-associated mutant R173W, indicating that the formation of ES3 is inhibited. The R173W crystal structure in the ES2-state revealed major rearrangements of the loops around the active site, compared to wild-type PBGD in the Eholo-state. These results contribute to elucidating the structural pathogenesis of two common AIP-associated mutations and reveal the important structural role of Arg173 in the polypyrrole elongation mechanism.en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titleCharacterization of porphobilinogen deaminase mutants reveals that arginine-173 is crucial for polypyrrole elongation mechanismen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2021 The Author(s)en_US
dc.source.articlenumber102152en_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.doi10.1016/j.isci.2021.102152
dc.identifier.cristin1916150
dc.source.journaliScienceen_US
dc.identifier.citationiScience. 2021, 24 (3), 102152.en_US
dc.source.volume24en_US
dc.source.issue3en_US


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Navngivelse 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse 4.0 Internasjonal