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PDBsum entry 4zdn
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References listed in PDB file
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Key reference
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Title
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Structural and evolutionary relationships of "at-Less" type i polyketide synthase ketosynthases.
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Authors
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J.R.Lohman,
M.Ma,
J.Osipiuk,
B.Nocek,
Y.Kim,
C.Chang,
M.Cuff,
J.Mack,
L.Bigelow,
H.Li,
M.Endres,
G.Babnigg,
A.Joachimiak,
G.N.Phillips,
B.Shen.
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Ref.
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Proc Natl Acad Sci U S A, 2015,
112,
12693-12698.
[DOI no: ]
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PubMed id
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Abstract
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Acyltransferase (AT)-less type I polyketide synthases (PKSs) break the type I
PKS paradigm. They lack the integrated AT domains within their modules and
instead use a discrete AT that acts in trans, whereas a type I PKS module
minimally contains AT, acyl carrier protein (ACP), and ketosynthase (KS)
domains. Structures of canonical type I PKS KS-AT didomains reveal structured
linkers that connect the two domains. AT-less type I PKS KSs have remnants of
these linkers, which have been hypothesized to be AT docking domains. Natural
products produced by AT-less type I PKSs are very complex because of an
increased representation of unique modifying domains. AT-less type I PKS KSs
possess substrate specificity and fall into phylogenetic clades that correlate
with their substrates, whereas canonical type I PKS KSs are monophyletic. We
have solved crystal structures of seven AT-less type I PKS KS domains that
represent various sequence clusters, revealing insight into the large structural
and subtle amino acid residue differences that lead to unique active site
topologies and substrate specificities. One set of structures represents a
larger group of KS domains from both canonical and AT-less type I PKSs that
accept amino acid-containing substrates. One structure has a partial AT-domain,
revealing the structural consequences of a type I PKS KS evolving into an
AT-less type I PKS KS. These structures highlight the structural diversity
within the AT-less type I PKS KS family, and most important, provide a unique
opportunity to study the molecular evolution of substrate specificity within the
type I PKSs.
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