PDBsum entry 4j1q

Oxidoreductase

PDB id: 4j1q

Contents

Protein chain

417 a.a.

Ligands

NDP

PDB id:

4j1q

Name:

Oxidoreductase

Title:

Crystal structure of a ketoreductase domain from the bacillaene assembly line

Structure:

Polyketide synthase pksj. Chain: a. Synonym: pks. Engineered: yes

Source:

Bacillus subtilis subsp. Subtilis. Organism_taxid: 224308. Strain: 168. Gene: bsu17180, pksj, pksj (amino acids 2669-3111), pksk. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.35Å R-factor: 0.233 R-free: 0.253

Authors:

J.Zheng,A.T.Keatinge-Clay

Key ref:

S.K.Piasecki et al. (2014). Structural and functional studies of a trans-acyltransferase polyketide assembly line enzyme that catalyzes stereoselective α- and β-ketoreduction. Proteins, 82, 2067-2077. PubMed id: 24634061 DOI: 10.1002/prot.24561

Date:

01-Feb-13 Release date: 19-Mar-14

Protein chain

P40806  (PKSJ_BACSU) -  Polyketide synthase PksJ from Bacillus subtilis (strain 168)

Seq: 5043 a.a.

Struc: 417 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.1.1.1.100 - 3-oxoacyl-[acyl-carrier-protein] reductase.
• Reaction: a (3R)-hydroxyacyl-[ACP] + NADP⁺ = a 3-oxoacyl-[ACP] + NADPH + H⁺

(3R)-hydroxyacyl-[ACP] + NADP(+) (Bound ligand (Het Group name = NDP) corresponds exactly) = 3-oxoacyl-[ACP] + NADPH + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1002/prot.24561

Proteins 82:2067-2077 (2014)

PubMed id: 24634061

Structural and functional studies of a trans-acyltransferase polyketide assembly line enzyme that catalyzes stereoselective α- and β-ketoreduction.

S.K.Piasecki, J.Zheng, A.J.Axelrod, M.E.Detelich, A.T.Keatinge-Clay.

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.