PDBsum entry 4yuc

Hydrolase

PDB id: 4yuc

Contents

Protein chain

330 a.a.

Ligands

MPD

Metals

_NA

Waters ×332

PDB id:

4yuc

Name:

Hydrolase

Title:

Crystal structure of corb derivatized with s-(2-acetamidoethyl) 4- methyl-3-oxohexanethioate

Structure:

Corb. Chain: a. Engineered: yes

Source:

Corallococcus coralloides. Organism_taxid: 184914. Gene: corb. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.31Å R-factor: 0.175 R-free: 0.187

Authors:

G.Zocher,J.Vilstrup,T.Stehle

Key ref:

G.Zocher et al. (2015). Structural basis of head to head polyketide fusion by CorB. Chem Sci, 6, 6525-6536. PubMed id: 28757960

Date:

18-Mar-15 Release date: 30-Mar-16

Protein chain

D7RK32  (D7RK32_CORCK) -  3-oxoacyl-(Acyl-carrier-protein) synthase III from Corallococcus coralloides

Seq: 335 a.a.

Struc: 330 a.a.

Chem Sci 6:6525-6536 (2015)

PubMed id: 28757960

Structural basis of head to head polyketide fusion by CorB.

G.Zocher, J.Vilstrup, D.Heine, A.Hallab, E.Goralski, C.Hertweck, M.Stahl, T.F.Schäberle, T.Stehle.

ABSTRACT

Corallopyronin A is a polyketide derived from the myxobacteriumCorallococcus coralloideswith potent antibiotic features. The gene cluster responsible for the biosynthesis of corallopyronin A has been described recently, and it was proposed that CorB acts as a ketosynthase to interconnect two polyketide chains in a rare head-to-head condensation reaction. We determined the structure of CorB, the interconnecting polyketide synthase, to high resolution and found that CorB displays a thiolase fold. Site-directed mutagenesis showed that the catalytic triad consisting of a cysteine, a histidine and an asparagine is crucial for catalysis, and that this triad shares similarities with the triad found in HMG-CoA synthases. We synthesized a substrate mimic to derivatize purified CorB and confirmed substrate attachment by ESI-MS. Structural analysis of the complex yielded an electron density-based model for the polyketide chain and showed that the unusually wide, T-shaped active site is able to accommodate two polyketides simultaneously. Our structural analysis provides a platform for understanding the unusual head-to-head polyketide-interconnecting reaction catalyzed by CorB.