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PDBsum entry 2ron
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* Residue conservation analysis
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PDB id:
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Hydrolase
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Title:
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The external thioesterase of the surfactin-synthetase
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Structure:
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Surfactin synthetase thioesterase subunit. Chain: a. Synonym: cold shock protein csi16. Engineered: yes
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Source:
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Bacillus subtilis. Organism_taxid: 1423. Gene: srfad. Expressed in: escherichia coli. Expression_system_taxid: 562.
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NMR struc:
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20 models
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Authors:
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A.Koglin,F.Lohr,F.Bernhard,V.V.Rogov,D.P.Frueh,E.R.Strieter, M.R.Mofid,P.Guentert,G.Wagner,C.T.Walsh,M.A.Marahiel,V.Doetsch
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Key ref:
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A.Koglin
et al.
(2008).
Structural basis for the selectivity of the external thioesterase of the surfactin synthetase.
Nature,
454,
907-911.
PubMed id:
DOI:
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Date:
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04-Apr-08
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Release date:
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12-Aug-08
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PROCHECK
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Headers
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References
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Q08788
(SRFAD_BACSU) -
Surfactin synthase thioesterase subunit from Bacillus subtilis (strain 168)
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Seq:
Struc:
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242 a.a.
242 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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DOI no:
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Nature
454:907-911
(2008)
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PubMed id:
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Structural basis for the selectivity of the external thioesterase of the surfactin synthetase.
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A.Koglin,
F.Löhr,
F.Bernhard,
V.V.Rogov,
D.P.Frueh,
E.R.Strieter,
M.R.Mofid,
P.Güntert,
G.Wagner,
C.T.Walsh,
M.A.Marahiel,
V.Dötsch.
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ABSTRACT
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Non-ribosomal peptide synthetases (NRPS) and polyketide synthases (PKS) found in
bacteria, fungi and plants use two different types of thioesterases for the
production of highly active biological compounds. Type I thioesterases (TEI)
catalyse the release step from the assembly line of the final product where it
is transported from one reaction centre to the next as a thioester linked to a
4'-phosphopantetheine (4'-PP) cofactor that is covalently attached to thiolation
(T) domains. The second enzyme involved in the synthesis of these secondary
metabolites, the type II thioesterase (TEII), is a crucial repair enzyme for the
regeneration of functional 4'-PP cofactors of holo-T domains of NRPS and PKS
systems. Mispriming of 4'-PP cofactors by acetyl- and short-chain acyl-residues
interrupts the biosynthetic system. This repair reaction is very important,
because roughly 80% of CoA, the precursor of the 4'-PP cofactor, is acetylated
in bacteria. Here we report the three-dimensional structure of a type II
thioesterase from Bacillus subtilis free and in complex with a T domain.
Comparison with structures of TEI enzymes shows the basis for substrate
selectivity and the different modes of interaction of TEII and TEI enzymes with
T domains. Furthermore, we show that the TEII enzyme exists in several
conformations of which only one is selected on interaction with its native
substrate, a modified holo-T domain.
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Selected figure(s)
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Figure 1.
Figure 1: Assembly line of the surfactin non-ribosomal peptide
synthetase. The surfactin synthetase consists of the three
subunits SrfA-A, SrfA-B and SrfA-C that together comprise seven
modules, each being responsible for the incorporation of one
amino acid residue. The release of the lipoheptapeptide is
catalysed by TEI attached to SrfC (module 7). The function of
SrfD, the external thioesterase TEII (lower left), is the
recycling of misprimed T domains. The 4'-PP cofactor is depicted
shortened, attached to the T domains. Ac, acetyl.
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Figure 3.
Figure 3: Complex structure of SrfTEII and the TycC3 T domain.
a, Interaction surfaces (red) for SrfTEII (top) and the TycC3 T
domain (bottom) are based on chemical shift perturbations
observed in NMR titration experiments of ^15N-labelled Ser86Ala
SrfTEII with unlabelled acetyl-holo-T domain and vice versa. The
interaction surface identified on the T domain is identical to
results published previously^5. b, Ribbon diagram of the refined
average structure of the complex of SrfTEII and the TycC3 T
domain calculated using the simulated annealing protocol of
CNS1.1. Surfaces are displayed only for the residues of SrfTEII
(blue) and the TycC3 T domain (red) showing intermolecular NOEs.
Residues showing chemical shift changes are coloured in the
ribbon diagrams accordingly. Some of the active site residues of
the TEII triad (Ser 86 and His 216) and the modified T domain
active site (Ser 45-4'-PP) showed very severe line broadening
(Supplementary Figs 3 and 4). The position of the 4'-PP cofactor
shown is based on the position in the free H state of the TycC3
peptidyl carrier protein (TycC3–PCP)^5.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2008,
454,
907-911)
copyright 2008.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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B.E.Alber
(2011).
Biotechnological potential of the ethylmalonyl-CoA pathway.
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Appl Microbiol Biotechnol,
89,
17-25.
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D.López,
and
R.Kolter
(2010).
Extracellular signals that define distinct and coexisting cell fates in Bacillus subtilis.
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FEMS Microbiol Rev,
34,
134-149.
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F.I.Kraas,
V.Helmetag,
M.Wittmann,
M.Strieker,
and
M.A.Marahiel
(2010).
Functional dissection of surfactin synthetase initiation module reveals insights into the mechanism of lipoinitiation.
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Chem Biol,
17,
872-880.
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H.J.Imker,
D.Krahn,
J.Clerc,
M.Kaiser,
and
C.T.Walsh
(2010).
N-acylation during glidobactin biosynthesis by the tridomain nonribosomal peptide synthetase module GlbF.
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Chem Biol,
17,
1077-1083.
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I.Sainis,
D.Fokas,
K.Vareli,
A.G.Tzakos,
V.Kounnis,
and
E.Briasoulis
(2010).
Cyanobacterial cyclopeptides as lead compounds to novel targeted cancer drugs.
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Mar Drugs,
8,
629-657.
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J.M.Crawford,
and
C.A.Townsend
(2010).
New insights into the formation of fungal aromatic polyketides.
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Nat Rev Microbiol,
8,
879-889.
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L.Du,
and
L.Lou
(2010).
PKS and NRPS release mechanisms.
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Nat Prod Rep,
27,
255-278.
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S.Kapur,
A.Y.Chen,
D.E.Cane,
and
C.Khosla
(2010).
Molecular recognition between ketosynthase and acyl carrier protein domains of the 6-deoxyerythronolide B synthase.
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Proc Natl Acad Sci U S A,
107,
22066-22071.
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T.P.Korman,
J.M.Crawford,
J.W.Labonte,
A.G.Newman,
J.Wong,
C.A.Townsend,
and
S.C.Tsai
(2010).
Structure and function of an iterative polyketide synthase thioesterase domain catalyzing Claisen cyclization in aflatoxin biosynthesis.
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Proc Natl Acad Sci U S A,
107,
6246-6251.
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PDB code:
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Z.X.Liang
(2010).
Complexity and simplicity in the biosynthesis of enediyne natural products.
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Nat Prod Rep,
27,
499-528.
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A.Koglin,
and
C.T.Walsh
(2009).
Structural insights into nonribosomal peptide enzymatic assembly lines.
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Nat Prod Rep,
26,
987.
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A.M.Gulick
(2009).
Conformational dynamics in the Acyl-CoA synthetases, adenylation domains of non-ribosomal peptide synthetases, and firefly luciferase.
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ACS Chem Biol,
4,
811-827.
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C.Khosla,
S.Kapur,
and
D.E.Cane
(2009).
Revisiting the modularity of modular polyketide synthases.
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Curr Opin Chem Biol,
13,
135-143.
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D.D.Boehr,
R.Nussinov,
and
P.E.Wright
(2009).
The role of dynamic conformational ensembles in biomolecular recognition.
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Nat Chem Biol,
5,
789-796.
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H.B.Claxton,
D.L.Akey,
M.K.Silver,
S.J.Admiraal,
and
J.L.Smith
(2009).
Structure and Functional Analysis of RifR, the Type II Thioesterase from the Rifamycin Biosynthetic Pathway.
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J Biol Chem,
284,
5021-5029.
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PDB codes:
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K.Watanabe,
H.Oguri,
and
H.Oikawa
(2009).
Diversification of echinomycin molecular structure by way of chemoenzymatic synthesis and heterologous expression of the engineered echinomycin biosynthetic pathway.
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Curr Opin Chem Biol,
13,
189-196.
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M.Kotaka,
R.Kong,
I.Qureshi,
Q.S.Ho,
H.Sun,
C.W.Liew,
L.P.Goh,
P.Cheung,
Y.Mu,
J.Lescar,
and
Z.X.Liang
(2009).
Structure and catalytic mechanism of the thioesterase CalE7 in enediyne biosynthesis.
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J Biol Chem,
284,
15739-15749.
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PDB code:
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M.Kotowska,
K.Pawlik,
A.Smulczyk-Krawczyszyn,
H.Bartosz-Bechowski,
and
K.Kuczek
(2009).
Type II thioesterase ScoT, associated with Streptomyces coelicolor A3(2) modular polyketide synthase Cpk, hydrolyzes acyl residues and has a preference for propionate.
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Appl Environ Microbiol,
75,
887-896.
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M.Strieker,
E.M.Nolan,
C.T.Walsh,
and
M.A.Marahiel
(2009).
Stereospecific synthesis of threo- and erythro-beta-hydroxyglutamic acid during kutzneride biosynthesis.
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J Am Chem Soc,
131,
13523-13530.
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P.Beltran-Alvarez,
C.J.Arthur,
R.J.Cox,
J.Crosby,
M.P.Crump,
and
T.J.Simpson
(2009).
Preliminary kinetic analysis of acyl carrier protein-ketoacylsynthase interactions in the actinorhodin minimal polyketide synthase.
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Mol Biosyst,
5,
511-518.
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P.Bernhardt,
and
S.E.O'Connor
(2009).
Opportunities for enzyme engineering in natural product biosynthesis.
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Curr Opin Chem Biol,
13,
35-42.
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S.K.Parker,
R.M.Barkley,
J.G.Rino,
and
M.L.Vasil
(2009).
Mycobacterium tuberculosis Rv3802c encodes a phospholipase/thioesterase and is inhibited by the antimycobacterial agent tetrahydrolipstatin.
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PLoS ONE,
4,
e4281.
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T.Wlodarski,
and
B.Zagrovic
(2009).
Conformational selection and induced fit mechanism underlie specificity in noncovalent interactions with ubiquitin.
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Proc Natl Acad Sci U S A,
106,
19346-19351.
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W.J.Ke,
B.Y.Chang,
T.P.Lin,
and
S.T.Liu
(2009).
Activation of the promoter of the fengycin synthetase operon by the UP element.
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J Bacteriol,
191,
4615-4623.
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S.Kapur,
and
C.Khosla
(2008).
Biochemistry: Fit for an enzyme.
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Nature,
454,
832-833.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
