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|Title:||Structural studies of geosmin synthase, a bifunctional sesquiterpene synthase with ?? domain architecture that catalyzes a unique cyclization-fragmentation reaction sequence||Authors:||Harris, Golda G.
Lombardi, Patrick M.
Pemberton, Travis A.
Weiss, Thomas M.
Cole, Kathryn E.
Murphy, Frank V.
Vedula, L. Sangeetha
Chou, Wayne K. W.
Cane, David E.
Christianson, David W.
|Issue Date:||Dec-2015||Publisher:||American Chemical Society||Source:||Harris, G. G., Lombardi, P. M., Pemberton, T. A., Matsui, T., Weiss, T. M., Cole, K. E., Köksal, M., ...Christianson, D. W. (2015). Structural studies of geosmin synthase, a bifunctional sesquiterpene synthase with αα domain architecture that catalyzes a unique cyclization-fragmentation reaction sequence. Biochemistry, 54(48), 7142-7155. doi:10.1021/acs.biochem.5b01143||Abstract:||Geosmin synthase from Streptomyces coelicolor (ScGS) catalyzes an unusual, metal-dependent terpenoid cyclization and fragmentation reaction sequence. Two distinct active sites are required for catalysis: the N-terminal domain catalyzes the ionization and cyclization of farnesyl diphosphate to form germacradienol and inorganic pyrophosphate (PPi), and the C-terminal domain catalyzes the protonation, cyclization, and fragmentation of germacradienol to form geosmin and acetone through a retro-Prins reaction. A unique αα domain architecture is predicted for ScGS based on amino acid sequence: each domain contains the metal-binding motifs typical of a class I terpenoid cyclase, and each domain requires Mg2+ for catalysis. Here, we report the X-ray crystal structure of the unliganded N-terminal domain of ScGS and the structure of its complex with three Mg2+ ions and alendronate. These structures highlight conformational changes required for active site closure and catalysis. Although neither full-length ScGS nor constructs of the C-terminal domain could be crystallized, homology models of the C-terminal domain were constructed on the basis of 36% sequence identity with the N-terminal domain. Small-angle X-ray scattering experiments yield low-resolution molecular envelopes into which the N-terminal domain crystal structure and the C-terminal domain homology model were fit, suggesting possible αα domain architectures as frameworks for bifunctional catalysis. © 2015 American Chemical Society.||URI:||http://doi.org/10.1021/acs.biochem.5b01143
|Appears in Collections:||Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik|
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Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
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