PDBsum entry 4u3v

Isomerase

PDB id: 4u3v

Contents

Protein chain

242 a.a.

Waters ×131

PDB id:

4u3v

Name:

Isomerase

Title:

Crystal structure of the trans-acyltransferase polyketide synthase enoyl-isomerase

Structure:

Polyketide synthase pksr. Chain: a. Fragment: unp residues 1124-1395. Engineered: yes

Source:

Bacillus subtilis. Organism_taxid: 224308. Strain: 168. Gene: pksr, bsu17220. Expressed in: escherichia coli. Expression_system_taxid: 511693. Expression_system_cell_line: bl21.

Resolution:

1.73Å R-factor: 0.215 R-free: 0.239

Authors:

D.C.Gay,P.J.Spear,A.T.Keatinge-Clay

Key ref:

D.C.Gay et al. (2014). A double-hotdog with a new trick: structure and mechanism of the trans-acyltransferase polyketide synthase enoyl-isomerase. Acs Chem Biol, 9, 2374-2381. PubMed id: 25089587 DOI: 10.1021/cb500459b

Date:

22-Jul-14 Release date: 20-Aug-14

Protein chain

O31784  (PKSR_BACSU) -  Polyketide synthase PksR from Bacillus subtilis (strain 168)

Seq: 2543 a.a.

Struc: 242 a.a.

Enzyme reactions

• Enzyme class: E.C.2.3.1.- - ?????

DOI no: 10.1021/cb500459b

Acs Chem Biol 9:2374-2381 (2014)

PubMed id: 25089587

A double-hotdog with a new trick: structure and mechanism of the trans-acyltransferase polyketide synthase enoyl-isomerase.

D.C.Gay, P.J.Spear, A.T.Keatinge-Clay.

ABSTRACT

Many polyketide natural products exhibit invaluable medicinal properties, yet much remains to be understood regarding the machinery responsible for their biosynthesis. The recently discovered trans-acyltransferase polyketide synthases employ processing enzymes that catalyze modifications unique from those of the classical cis-acyltransferase polyketide synthases. The enoyl-isomerase domains of these megasynthases shift double bonds and are well-represented by an enzyme that helps forge the triene system within the antibiotic produced by the prototypical bacillaene synthase. This first crystal structure of an enoyl-isomerase, at 1.73 Å resolution, not only revealed relationships between this class of enzymes and dehydratases but also guided an investigation into the mechanism of double bond migration. The catalytic histidine, positioned differently from that of dehydratases, was demonstrated to independently shuttle a proton between the γ- and α-positions of the intermediate. This unprecedented mechanism highlights the catalytic diversity of divergent enzymes within trans-acyltransferase polyketide synthases.