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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.
Matsui, Tsutomu
Weiss, Thomas M.
Cole, Kathryn E.
Köksal, Mustafa
Murphy, Frank V.
Vedula, L. Sangeetha
Chou, Wayne K. W.
Cane, David E.
Christianson, David W.
Keywords: Cyclization
Streptomyces coelicolor
Crystal structure
Geosmin synthase
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.
ISSN: 0006-2960
Appears in Collections:Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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