 |
PDBsum entry 4j1q
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Oxidoreductase
|
PDB id
|
|
|
|
4j1q
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structural and functional studies of a trans-Acyltransferase polyketide assembly line enzyme that catalyzes stereoselective α- And β-Ketoreduction.
|
|
|
Authors
|
|
S.K.Piasecki,
J.Zheng,
A.J.Axelrod,
M.E.Detelich,
A.T.Keatinge-Clay.
|
|
|
Ref.
|
|
Proteins, 2014,
82,
2067-2077.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Abstract
|
|
|
While the cis-acyltransferase modular polyketide synthase assembly lines have
largely been structurally dissected, enzymes from within the recently discovered
trans-acyltransferase polyketide synthase assembly lines are just starting to be
observed crystallographically. Here we examine the ketoreductase (KR) from the
first polyketide synthase module of the bacillaene nonribosomal peptide
synthetase/polyketide synthase at 2.35-Å resolution. This KR naturally reduces
both α- and β-keto groups and is the only KR known to do so during the
biosynthesis of a polyketide. The isolated KR not only reduced an
N-acetylcysteamine-bound β-keto substrate to a D-β-hydroxy product, but also
an N-acetylcysteamine-bound α-keto substrate to an L-α-hydroxy product. That
the substrates must enter the active site from opposite directions to generate
these stereochemistries suggests that the acyl-phosphopantetheine moiety is
capable of accessing very different conformations despite being anchored to a
serine residue of a docked acyl carrier protein. The features enabling
stereocontrolled α-ketoreduction may not be extensive since a KR that naturally
reduces a β-keto group within a cis-acyltransferase polyketide synthase was
identified that performs a completely stereoselective reduction of the same
α-keto substrate to generate the D-α-hydroxy product. A sequence analysis of
trans-acyltransferase KRs reveals that a single residue, rather than a
three-residue motif found in cis-acyltransferase KRs, is predictive of the
orientation of the resulting β-hydroxyl group. Proteins 2014; 82:2067-2077. ©
2014 Wiley Periodicals, Inc.
|
|
|
|
|
|
|
