PDBsum entry 5dz2

Lyase

PDB id: 5dz2

Contents

Protein chains

322 a.a.

Ligands

212 ×2

Metals

_MG ×6

Waters ×145

PDB id:

5dz2

Name:

Lyase

Title:

Geosmin synthase from streptomyces coelicolor n-terminal domain complexed with three mg2+ ions and alendronic acid

Structure:

Germacradienol/geosmin synthase. Chain: a, b. Fragment: n-terminal domain (unp residues 1-338). Synonym: scgs. Engineered: yes

Source:

Streptomyces coelicolor (strain atcc baa-471 / a3(2) / m145). Organism_taxid: 100226. Strain: atcc baa-471 / a3(2) / m145. Gene: cyc2, sco6073, sc9b1.20. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.11Å R-factor: 0.210 R-free: 0.250

Authors:

G.G.Harris,P.M.Lombardi,T.A.Pemberton,T.Matsui,T.M.Weiss,K.E.Cole, M.Koksal,F.V.Murphy,L.S.Vedula,W.K.W.Chou,D.E.Cane,D.W.Christianson

Key ref:

G.G.Harris et al. (2015). Structural Studies of Geosmin Synthase, a Bifunctional Sesquiterpene Synthase with αα Domain Architecture That Catalyzes a Unique Cyclization-Fragmentation Reaction Sequence. Biochemistry, 54, 7142-7155. PubMed id: 26598179 DOI: 10.1021/acs.biochem.5b01143

Date:

25-Sep-15 Release date: 09-Dec-15

Protein chains

Q9X839  (CYC2_STRCO) -  Germacradienol/geosmin synthase from Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145)

Seq: 726 a.a.

Struc: 322 a.a.

Enzyme reactions

• Enzyme class 2: E.C.4.1.99.16 - geosmin synthase.
• Reaction: (1E,4S,5E,7R)-germacra-1₁₀,5-dien-11-ol + H2O = ^--geosmin + acetone
• Cofactor: Mg(2+)
• Enzyme class 3: E.C.4.2.3.22 - germacradienol synthase.
• Reaction: (2E,6E)-farnesyl diphosphate + H2O = (1E,4S,5E,7R)-germacra-1₁₀,5-dien- 11-ol + diphosphate
• Cofactor: Mg(2+)
• Enzyme class 4: E.C.4.2.3.75 - (-)-germacrene D synthase.
• Reaction: (2E,6E)-farnesyl diphosphate = ^--germacrene D + diphosphate

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1021/acs.biochem.5b01143

Biochemistry 54:7142-7155 (2015)

PubMed id: 26598179

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

G.G.Harris, P.M.Lombardi, T.A.Pemberton, T.Matsui, T.M.Weiss, K.E.Cole, M.Köksal, F.V.Murphy, L.S.Vedula, W.K.Chou, D.E.Cane, D.W.Christianson.

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.