PDBsum entry 1tee

Transferase

PDB id: 1tee

Contents

Protein chains

368 a.a. *

* Residue conservation analysis

PDB id:

1tee

Name:

Transferase

Title:

Crystal structure of c205f mutant of pks18 from mycobacterium tuberculosis

Structure:

Pks18. Chain: a, b, c, d. Synonym: polyketide synthase. Engineered: yes. Mutation: yes

Source:

Mycobacterium tuberculosis. Organism_taxid: 83332. Strain: h37rv. Gene: pks18. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PQS)

Resolution:

2.90Å R-factor: 0.221 R-free: 0.258

Authors:

R.Sankaranarayanan,V.M.Shanmugam,R.Rukmini

Key ref:

R.Sankaranarayanan et al. (2004). A novel tunnel in mycobacterial type III polyketide synthase reveals the structural basis for generating diverse metabolites. Nat Struct Mol Biol, 11, 894-900. PubMed id: 15286723 DOI: 10.1038/nsmb809

Date:

25-May-04 Release date: 03-Aug-04

Protein chains

P9WPF1  (PKS18_MYCTU) -  Alpha-pyrone synthesis polyketide synthase-like Pks18 from Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)

Seq: 393 a.a.

Struc: 368 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.2.3.1.- - ?????

DOI no: 10.1038/nsmb809

Nat Struct Mol Biol 11:894-900 (2004)

PubMed id: 15286723

A novel tunnel in mycobacterial type III polyketide synthase reveals the structural basis for generating diverse metabolites.

R.Sankaranarayanan, P.Saxena, U.B.Marathe, R.S.Gokhale, V.M.Shanmugam, R.Rukmini.

ABSTRACT

The superfamily of plant and bacterial type III polyketide synthases (PKSs) produces diverse metabolites with distinct biological functions. PKS18, a type III PKS from Mycobacterium tuberculosis, displays an unusual broad specificity for aliphatic long-chain acyl-coenzyme A (acyl-CoA) starter units (C(6)-C(20)) to produce tri- and tetraketide pyrones. The crystal structure of PKS18 reveals a 20 A substrate binding tunnel, hitherto unidentified in this superfamily of enzymes. This remarkable tunnel extends from the active site to the surface of the protein and is primarily generated by subtle changes of backbone dihedral angles in the core of the protein. Mutagenic studies combined with structure determination provide molecular insights into the structural elements that contribute to the chain length specificity of the enzyme. This first bacterial type III PKS structure underlines a fascinating example of the way in which subtle changes in protein architecture can generate metabolite diversity in nature.

Selected figure(s)

Figure 1.
Figure 1. A schematic diagram of the reaction catalyzed by PKS18.

Figure 5.
Figure 5. C205F mutant structure. A closeup view of the residues surrounding the substrate binding tunnel shown in a stereo representation. The phenylalanine residue is shown with the electron density, a 2F[o] - F[c] map contoured at 1.2 , along with a stick model of the myristic acid moiety as observed in the wild type structure. Figure was prepared using SETOR34.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2004, 11, 894-900) copyright 2004.

Figures were selected by an automated process.