5DZ2

Geosmin synthase from Streptomyces coelicolor N-terminal domain complexed with three Mg2+ ions and alendronic acid

Summary for 5DZ2

• Entry DOI: 10.2210/pdb5dz2/pdb
• Related: 5DW7
• Descriptor: Germacradienol/geosmin synthase, MAGNESIUM ION, ALENDRONATE, ... (4 entities in total)
• Functional Keywords: terpene, cyclase, geosmin, germacradienol, lyase
• Biological source: Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145)
• Total number of polymer chains: 2
• Total formula weight: 77177.80

Authors

Harris, G.G.,Lombardi, P.M.,Pemberton, T.A.,Matsui, T.,Weiss, T.M.,Cole, K.E.,Koksal, M.,Murphy, F.V.,Vedula, L.S.,Chou, W.K.W.,Cane, D.E.,Christianson, D.W. (deposition date: 2015-09-25, release date: 2015-12-09, Last modification date: 2023-09-27)

Primary citation

Harris, G.G.,Lombardi, P.M.,Pemberton, T.A.,Matsui, T.,Weiss, T.M.,Cole, K.E.,Koksal, M.,Murphy, F.V.,Vedula, L.S.,Chou, W.K.,Cane, D.E.,Christianson, D.W.
Structural Studies of Geosmin Synthase, a Bifunctional Sesquiterpene Synthase with alpha alpha Domain Architecture That Catalyzes a Unique Cyclization-Fragmentation Reaction Sequence.
Biochemistry, 54:7142-7155, 2015

PubMed 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 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 αα domain architectures as frameworks for bifunctional catalysis.

PubMed: 26598179
DOI: 10.1021/acs.biochem.5b01143

Experimental method

X-RAY DIFFRACTION (2.111 Å)