Structural highlights
Function
[PKS18_MYCTO] Involved in the biosynthesis of tri- and tetraketide alpha-pyrones. Pks18 catalyzes the extension of medium- and long-chain aliphatic acyl-CoA substrates by using malonyl-CoA as an extender molecule to synthesize polyketide products (By similarity).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
A novel tunnel in mycobacterial type III polyketide synthase reveals the structural basis for generating diverse metabolites.,Sankaranarayanan R, Saxena P, Marathe UB, Gokhale RS, Shanmugam VM, Rukmini R Nat Struct Mol Biol. 2004 Sep;11(9):894-900. Epub 2004 Aug 1. PMID:15286723[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sankaranarayanan R, Saxena P, Marathe UB, Gokhale RS, Shanmugam VM, Rukmini R. A novel tunnel in mycobacterial type III polyketide synthase reveals the structural basis for generating diverse metabolites. Nat Struct Mol Biol. 2004 Sep;11(9):894-900. Epub 2004 Aug 1. PMID:15286723 doi:10.1038/nsmb809
