PDBsum entry 4jap

Transferase

PDB id: 4jap

Contents

Protein chains

352 a.a.

Ligands

PLM ×2

COA ×2

14U ×2

Waters ×185

PDB id:

4jap

Name:

Transferase

Title:

Crystal structure of mycobacterium tuberculosis pks11 reveals intermediates in the synthesis of methyl-branched alkylpyrones

Structure:

Alpha-pyrone synthesis polyketide synthase-like pks11. Chain: d, c, b, a. Synonym: alpha-pyrone synthesis polyketide synthase type iii pks11, chalcone synthase-like protein, chs-like. Engineered: yes

Source:

Mycobacterium tuberculosis. Organism_taxid: 1773. Strain: h37rv. Gene: pks11, rv1665, mt1705. Expressed in: mycobacterium smegmatis. Expression_system_taxid: 1772

Resolution:

1.83Å R-factor: 0.237 R-free: 0.289

Authors:

K.Gokulan,J.C.Sacchettini,Mycobacterium Tuberculosis Structural Proteomics Project (Xmtb)

Key ref:

K.Gokulan et al. (2013). Crystal structure of Mycobacterium tuberculosis polyketide synthase 11 (PKS11) reveals intermediates in the synthesis of methyl-branched alkylpyrones. J Biol Chem, 288, 16484-16494. PubMed id: 23615910 DOI: 10.1074/jbc.M113.468892

Date:

19-Feb-13 Release date: 24-Apr-13

Protein chains

P9WPF3  (PKS11_MYCTU) -  Methyl-branched alkylpyrone synthesis polyketide synthase-like Pks11 from Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)

Seq: 353 a.a.

Struc: 352 a.a.

Enzyme reactions

• Enzyme class: E.C.2.3.1.- - ?????

DOI no: 10.1074/jbc.M113.468892

J Biol Chem 288:16484-16494 (2013)

PubMed id: 23615910

Crystal structure of Mycobacterium tuberculosis polyketide synthase 11 (PKS11) reveals intermediates in the synthesis of methyl-branched alkylpyrones.

K.Gokulan, S.E.O'Leary, W.K.Russell, D.H.Russell, M.Lalgondar, T.P.Begley, T.R.Ioerger, J.C.Sacchettini.

ABSTRACT

PKS11 is one of three type III polyketide synthases (PKSs) identified in Mycobacterium tuberculosis. Although many PKSs in M. tuberculosis have been implicated in producing complex cell wall glycolipids, the biological function of PKS11 is unknown. PKS11 has previously been proposed to synthesize alkylpyrones from fatty acid substrates. We solved the crystal structure of M. tuberculosis PKS11 and found the overall fold to be similar to other type III PKSs. PKS11 has a deep hydrophobic tunnel proximal to the active site Cys-138 to accommodate substrates. We observed electron density in this tunnel from a co-purified molecule that was identified by mass spectrometry to be palmitate. Co-crystallization with malonyl-CoA (MCoA) or methylmalonyl-CoA (MMCoA) led to partial turnover of the substrate, resulting in trapped intermediates. Reconstitution of the reaction in solution confirmed that both co-factors are required for optimal activity, and kinetic analysis shows that MMCoA is incorporated first, then MCoA, followed by lactonization to produce methyl-branched alkylpyrones.