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dc.contributor.authorCorless, Elliot I.
dc.contributor.authorImran, Syed Muhammad Saad
dc.contributor.authorWatkins, Maxwell B.
dc.contributor.authorBacik, John-Paul
dc.contributor.authorMattice, Jenna
dc.contributor.authorPatterson, Angela
dc.contributor.authorDanyal, Karamatullah
dc.contributor.authorSoffe, Mark
dc.contributor.authorKitelinger, Robert
dc.contributor.authorSeefeldt, Lance C.
dc.contributor.authorOriganti, Sofia S.
dc.contributor.authorBennett, Brian
dc.contributor.authorBothner, Brian
dc.contributor.authorAndo, Nozomi
dc.contributor.authorAntony, Edwin
dc.date.accessioned2022-06-06T22:23:35Z
dc.date.available2022-06-06T22:23:35Z
dc.date.issued2020-11
dc.identifier.citationCorless, E. I., Imran, S. M. S., Watkins, M. B., Bacik, J. P., Mattice, J. R., Patterson, A., ... & Antony, E. (2021). The flexible N-terminus of BchL autoinhibits activity through interaction with its [4Fe-4S] cluster and released upon ATP binding. Journal of Biological Chemistry, 296.en_US
dc.identifier.issn0021-9258
dc.identifier.urihttps://scholarworks.montana.edu/xmlui/handle/1/16822
dc.description.abstractA key step in bacteriochlorophyll biosynthesis is the reduction of protochlorophyllide to chlorophyllide, catalyzed by dark-operative protochlorophyllide oxidoreductase (DPOR). DPOR contains two [4Fe-4S]-containing component proteins (BchL and BchNB) that assemble upon ATP binding to BchL to coordinate electron transfer and protochlorophyllide reduction. But the precise nature of the ATP-induced conformational changes are poorly understood. We present a crystal structure of BchL in the nucleotide-free form where a conserved, flexible region in the N-terminus masks the [4Fe-4S] cluster at the docking interface between BchL and BchNB. Amino acid substitutions in this region produce a hyper-active enzyme complex, suggesting a role for the N-terminus in auto-inhibition. Hydrogen deuterium exchange mass spectrometry shows that ATP-binding to BchL produces specific conformational changes leading to release of the flexible N-terminus from the docking interface. The release also promotes changes within the local environment surrounding the [4Fe-4S] cluster and promotes BchL complex formation with BchNB. A key patch of amino acids, Asp-Phe-Asp (the ‘DFD patch’), situated at the mouth of the BchL ATP-binding pocket promotes inter-subunit cross stabilization of the two subunits. A linked BchL dimer with one defective ATP-binding site does not support protochlorophyllide reduction, illustrating nucleotide binding to both subunits as a prerequisite for the inter-subunit cross stabilization. The masking of the [4Fe-4S] cluster by the flexible N-terminal region and the associated inhibition of activity is a novel mechanism of regulation in metalloproteins. Such mechanisms are possibly an adaptation to the anaerobic nature of eubacterial cells with poor tolerance for oxygen.en_US
dc.language.isoen_USen_US
dc.publisherElsevier BVen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleThe flexible N-terminus of BchL autoinhibits activity through interaction with its [4Fe-4S] cluster and relieved upon ATP bindingen_US
dc.typeArticleen_US
mus.citation.extentfirstpage1en_US
mus.citation.journaltitleJournal of Biological Chemistryen_US
mus.identifier.doi10.1074/jbc.RA120.016278en_US
mus.relation.collegeCollege of Letters & Scienceen_US
mus.relation.departmentChemistry & Biochemistry.en_US
mus.relation.universityMontana State University - Bozemanen_US


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