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Publication Abstract from PubMed

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 alphaalpha 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 approximately 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 alphaalpha domain architectures as frameworks for bifunctional catalysis.

Structural Studies of Geosmin Synthase, a Bifunctional Sesquiterpene Synthase with alphaalpha Domain Architecture That Catalyzes a Unique Cyclization-Fragmentation Reaction Sequence.,Harris GG, Lombardi PM, Pemberton TA, Matsui T, Weiss TM, Cole KE, Koksal M, Murphy FV 4th, Vedula LS, Chou WK, Cane DE, Christianson DW Biochemistry. 2015 Dec 8;54(48):7142-7155. Epub 2015 Nov 24. PMID:26598179^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.