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PDBsum entry 1dgp
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References listed in PDB file
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Key reference
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Title
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Crystal structure determination of aristolochene synthase from the blue cheese mold, Penicillium roqueforti.
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Authors
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J.M.Caruthers,
I.Kang,
M.J.Rynkiewicz,
D.E.Cane,
D.W.Christianson.
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Ref.
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J Biol Chem, 2000,
275,
25533-25539.
[DOI no: ]
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PubMed id
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Abstract
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The 2.5-A resolution crystal structure of recombinant aristolochene synthase
from the blue cheese mold, Penicillium roqueforti, is the first of a fungal
terpenoid cyclase. The structure of the enzyme reveals active site features that
participate in the cyclization of the universal sesquiterpene cyclase substrate,
farnesyl diphosphate, to form the bicyclic hydrocarbon aristolochene.
Metal-triggered carbocation formation initiates the cyclization cascade, which
proceeds through multiple complex intermediates to yield one exclusive
structural and stereochemical isomer of aristolochene. Structural homology of
this fungal cyclase with plant and bacterial terpenoid cyclases, despite minimal
amino acid sequence identity, suggests divergence from a common, primordial
ancestor in the evolution of terpene biosynthesis.
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Figure 4.
Fig. 4. Evolution of sesquiterpene biosynthetic pathways.
Structural comparison of terpenoid synthases reveals that each
enzyme in the biosynthetic pathway is a variation of the
"terpenoid synthase fold," despite insignificant amino acid
sequence identities. This structural comparison indicates
evolutionary divergence of animal, plant, bacterial, and fungal
cyclases from a common primordial ancestor.
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Figure 6.
Fig. 6. Structure-based mechanism of P. roqueforti
aristolochene synthase. Models of the enzyme complexed with
substrate, intermediates, and product are shown; salient
mechanistic details are outlined in the text and appear
schematically in Fig. 5. Briefly, farnesyl diphosphate binds in
the unique productive conformation prior to the departure of the
diphosphate leaving group (A). The initial cyclization yields
the germacrene A intermediate through formation of the C-1-C-10
bond (B) (the diphosphate leaving group is not shown for
clarity). Protonation of C-6 by Tyr-92 accompanied by C-2-C-7
bond formation closes the 10-membered ring of germacrene A to
form the bicyclic eudesmane cation intermediate (C). A
1,2-hydride transfer, accompanied by a C-14 methyl migration and
the elimination of H  8, yield
aristolochene (D). Figure prepared with AVS (44).
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2000,
275,
25533-25539)
copyright 2000.
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