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Structural Studies of Geosmin Synthase, a Bifunctional Sesquiterpene Synthase with ?? Domain Architecture That Catalyzes a Unique Cyclization-Fragmentation Reaction Sequence.


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 ?? 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 Mg(2+) 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 Mg(2+) 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 ?? domain architectures as frameworks for bifunctional catalysis.

SUBMITTER: Harris GG 

PROVIDER: S-EPMC4674366 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Structural Studies of Geosmin Synthase, a Bifunctional Sesquiterpene Synthase with αα Domain Architecture That Catalyzes a Unique Cyclization-Fragmentation Reaction Sequence.

Harris Golda G GG   Lombardi Patrick M PM   Pemberton Travis A TA   Matsui Tsutomu T   Weiss Thomas M TM   Cole Kathryn E KE   Köksal Mustafa M   Murphy Frank V FV   Vedula L Sangeetha LS   Chou Wayne K W WK   Cane David E DE   Christianson David W DW  

Biochemistry 20151124 48


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  ...[more]

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