Stereochemical disposition of the geminal dimethyl groups in the enzymatic cyclization of geranyl diphosphate to (+)-bornyl diphosphate by recombinant (+)-bornyl diphosphate synthase from Salvia officinalis

Wise, Mitchell L.; Pyun, Hyung‐Jung; Helms, Greg; Assink, Bryce; Coates, Robert M.; Croteau, Rodney

doi:10.1016/s0040-4020(01)00451-3

Cited by 23 publications

(31 citation statements)

References 34 publications

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“…5). The stereochemistry of this cyclization cascade is outlined in previous enzymological studies (32,33,(35)(36)(37)(38). On diphosphate recognition, diphosphate-triggered conformational changes trap GPP and water molecule #110 in the active site cavity.…”

Section: Structures Of Enzyme-ligand Complexesmentioning

confidence: 93%

Bornyl diphosphate synthase: Structure and strategy for carbocation manipulation by a terpenoid cyclase

Whittington

Wise

Urbanský

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

285

415

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The x-ray crystal structure of dimeric (؉)-bornyl diphosphate synthase, a metal-requiring monoterpene cyclase from Salvia officinalis, is reported at 2.0-Å resolution. Each monomer contains two ␣-helical domains: the C-terminal domain catalyzes the cyclization of geranyl diphosphate, orienting and stabilizing multiple reactive carbocation intermediates; the N-terminal domain has no clearly defined function, although its N terminus caps the active site in the C-terminal domain during catalysis. Structures of complexes with aza analogues of substrate and carbocation intermediates, as well as complexes with pyrophosphate and bornyl diphosphate, provide ''snapshots'' of the terpene cyclization cascade.

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Section: Structures Of Enzyme-ligand Complexesmentioning

confidence: 93%

Bornyl diphosphate synthase: Structure and strategy for carbocation manipulation by a terpenoid cyclase

Whittington

Wise

Urbanský

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

285

415

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“…The racemic tertiary alcohol (18, 42%) was separated from other products by silica gel chromatography and characterized by 1 H, 13 C and 19 F spectral data. (18) by the Cramer procedure [26][27][28] as modified by Danilov [29] and Assink [7,30] ((Bu 4 N) 2 HPO 4 , CCl 3 CN, CH 3 CN, 25°C, 30 min) (Scheme 2) followed by precipitation of inorganic ammonium salts (2% NH 3 in MeOH) and gradient ion exchange chromatography (NH 4 HCO 2 in MeOH) on a Dowex 1X8-400 column provided fractions containing monophosphate, diphosphate, and NH 4 HCO 2 . The ammonium formate was then removed by passage through an Amberlite XAD column with aq.…”

Section: Methodsmentioning

confidence: 99%

“…(3R)-and (3S)-Homolinalyl diphosphates (9 and 10) were prepared by Danilov-Cramer phosphorylations with (Bu 4 N)H 2 PO 4 (5 equiv,) and CCl 3 CN (30 equiv, CH 2 Cl 2 , 20 min) [7,29,30]. Removal of inorganic salts and separation of the monophosphates and diphosphates was accomplished as described above for 2-FLPP.…”

Section: Phosphorylation Of 2-fluorolinaloolmentioning

confidence: 99%

“…This version of the recombinant enzyme was truncated at R58, the approximate cleavage site for the plastid targeting sequence [39]. The cDNA encoding bornyl diphosphate synthase from sage (Salvia officinalis) [40] was also subcloned into the pSBET [38] vector, expressed in E. coli and purified (to ~98%) as previously described [7,12]. This version of the recombinant enzyme was similarly truncated at E50 to provide a pseudomature form devoid of the plastid transit peptide [9,12].…”

Section: Enzyme Preparationmentioning

confidence: 99%

“…These mechanistic features appear to be common to nearly all monoterpene cyclase transformations, with subsequent steps involving either termination of the reaction by deprotonation or nucleophile capture, or further electrophilic cyclizations via the remaining double bond, hydride shifts, or rearrangements before termination [1][2][3]. For example, direct deprotonation from the adjacent methyl of the (4S)-α-terpinyl cation (3b) yields (−)-limonene (4) [4,5], whereas C7-C1 bridging of the (4R)-α-terpinyl intermediate (3a) with capture of the resulting cation (5) by the paired diphosphate anion generates (+)-bornyl diphosphate (6) [6,7].…”

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confidence: 99%

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Inhibition of monoterpene cyclases by inert analogues of geranyl diphosphate and linalyl diphosphate

Karp

Zhao

Santhamma

et al. 2007

Archives of Biochemistry and Biophysics

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The tightly coupled nature of the reaction sequence catalyzed by monoterpene synthases has prevented direct observation of the topologically required isomerization step leading from geranyl diphosphate to the enzyme-bound, tertiary allylic intermediate linalyl diphosphate, which then cyclizes to the various monoterpene skeletons. X-ray crystal structures of these enzymes complexed with suitable analogues of the substrate and intermediate could provide a clearer view of this universal, but cryptic, step of monoterpenoid cyclase catalysis. Toward this end, the functionally inert analogues 2-fluorogeranyl diphosphate, (±)-2-fluorolinalyl diphosphate, and (3R)-and (3S)-homolinalyl diphosphates (2,6-dimethyl-2-vinyl-5-heptenyl diphosphates) were prepared, and compared to the previously described substrate analogue 3-azageranyl diphosphate (3-aza-2,3-dihydrogeranyl diphosphate) as inhibitors and potential crystallization aids with two representative monoterpenoid cyclases, (−)-limonene synthase and (+)-bornyl diphosphate synthase. Although these enantioselective synthases readily distinguished between (3R)-and (3S)-homolinalyl diphosphates, both of which were more effective inhibitors than was 3-azageranyl diphosphate, the fluorinated analogues proved to be the most potent competitive inhibitors and have recently yielded informative liganded structures with limonene synthase.

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Stereoselective Disposition of the Geminal Dimethyl Group in the Cyclization of Geranyl Acetate under Zeolite Confinement Conditions

Tsangarakis

Stratakis

2006

Eur J Org Chem

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The stereochemistry in the acid-catalysed biomimetic cyclization of [8,8,8-D 3 ]geranyl acetate was examined in solution and under conditions of zeolite Y confinement. In the intrazeolite reaction the gem-allylic methyl group adopts a diastereoselective disposition in the cyclization product (64 % dr). In contrast, the gem-dimethyl disposition in a homogeneous medium (ClSO 3 H/2-nitropropane) proceeds

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Stereochemical disposition of the geminal dimethyl groups in the enzymatic cyclization of geranyl diphosphate to (+)-bornyl diphosphate by recombinant (+)-bornyl diphosphate synthase from Salvia officinalis

Cited by 23 publications

References 34 publications

Bornyl diphosphate synthase: Structure and strategy for carbocation manipulation by a terpenoid cyclase

Bornyl diphosphate synthase: Structure and strategy for carbocation manipulation by a terpenoid cyclase

Inhibition of monoterpene cyclases by inert analogues of geranyl diphosphate and linalyl diphosphate

Stereoselective Disposition of the Geminal Dimethyl Group in the Cyclization of Geranyl Acetate under Zeolite Confinement Conditions

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