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PDBsum entry 2vsq
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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 of the termination module of a nonribosomal peptide synthetase.
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Authors
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A.Tanovic,
S.A.Samel,
L.O.Essen,
M.A.Marahiel.
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Ref.
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Science, 2008,
321,
659-663.
[DOI no: ]
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PubMed id
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Abstract
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Nonribosomal peptide synthetases (NRPSs) are modular multidomain enzymes that
act as an assembly line to catalyze the biosynthesis of complex natural
products. The crystal structure of the 144-kilodalton Bacillus subtilis
termination module SrfA-C was solved at 2.6 angstrom resolution. The adenylation
and condensation domains of SrfA-C associate closely to form a catalytic
platform, with their active sites on the same side of the platform. The peptidyl
carrier protein domain is flexibly tethered to this platform and thus can move
with its substrate-loaded 4'-phosphopantetheine arm between the active site of
the adenylation domain and the donor side of the condensation domain. The SrfA-C
crystal structure has implications for the rational redesign of NRPSs as a means
of producing novel bioactive peptides.
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Figure 1.
Fig. 1. Organization and overall structure of the synthetase
SrfA-C, the termination module of the surfactin biosynthesis
cluster from B. subtilis ATCC 21332. (A) The surfactin
biosynthetic operon [including srfA-A, 10,767 base pairs (bp);
srfA-B, 10,764 bp; srfA-C, 3825 bp] encoding the nonribosomal
peptide synthetases SrfA-A, B, and C and associated genes
(srfA-D and sfp). The chemical structure of the lipoheptapeptide
product surfactin is shown on the right. The yellow box
indicates the ring closure site between Leu^7 and the
β-hydroxyl group of the fatty acid catalyzed by SrfA-C. (B)
Schematic illustration of the terminal synthetase SrfA-C
comprising the condensation domain (C, gray), adenylation domain
(A, red and orange), peptidyl carrier protein domain (PCP,
green), and thioesterase domain (TE, brown). Linkers are blue;
the C-terminal tag helix is yellow. (C) Overall structure of
SrfA-C at 2.6 Å resolution. The C domain's catalytically
active residue His^147 and a leucine residue bound in the A
domain's active site are shown in space-filling representation.
Coloring of the domains is according to (B). See fig. S6 for
stereoviews of the total SrfA-C structure. All figures were made
with PYMOL 1.0 (20).
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Figure 5.
Fig. 5. Distances between the catalytic center of the PCP
domain at Ala^1003 and those of the C domain (His^147), the A
domain (Leu residue in the active site), and the TE domain
(Ser^1120), respectively. The dashed yellow circle has a radius
of 20 Å, corresponding to the distance that a
4'-phosphopantetheine cofactor can span. Because of perspective,
the interdomain distances appear shorter than they are.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2008,
321,
659-663)
copyright 2008.
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