2WGE

Crystal structure of KasA of Mycobacterium tuberculosis with bound TLM

Summary for 2WGE

• Entry DOI: 10.2210/pdb2wge/pdb
• Related: 2WGD 2WGF 2WGG
• Descriptor: 3-OXOACYL-[ACYL-CARRIER-PROTEIN] SYNTHASE 1, GLYCEROL, ISOPROPYL ALCOHOL, ... (6 entities in total)
• Functional Keywords: beta ketoacyl synthase i thiolactomycin, cytoplasm, transferase, acyltransferase, lipid synthesis, fatty acid biosynthesis
• Biological source: MYCOBACTERIUM TUBERCULOSIS
• Cellular location: Cytoplasm (Potential): P63454
• Total number of polymer chains: 1
• Total formula weight: 44298.02

Authors

Luckner, S.R.,Kisker, C. (deposition date: 2009-04-17, release date: 2009-07-21, Last modification date: 2023-12-13)

Primary citation

Luckner, S.R.,Machutta, C.A.,Tonge, P.J.,Kisker, C.
Crystal Structures of Mycobacterium Tuberculosis Kasa Show Mode of Action within Cell Wall Biosynthesis and its Inhibition by Thiolactomycin
Structure, 17:1004-, 2009

PubMed Abstract: Mycobacteria have a unique cell wall consisting of mycolic acids, very-long-chain lipids that provide protection and allow the bacteria to persist within human macrophages. Inhibition of cell wall biosynthesis is fatal for the organism and a starting point for the discovery and development of novel antibiotics. We determined the crystal structures of KasA, a key enzyme involved in the biosynthesis of long-chain fatty acids, in its apo-form and bound to the natural product inhibitor thiolactomycin. Detailed insights into the interaction of the inhibitor with KasA and the identification of a polyethylene glycol molecule that mimics a fatty acid substrate of approximately 40 carbon atoms length, represent the first atomic view of a mycobacterial enzyme involved in the synthesis of long-chain fatty acids and provide a robust platform for the development of novel thiolactomycin analogs with high affinity for KasA.

PubMed: 19604480
DOI: 10.1016/J.STR.2009.04.012

Experimental method

X-RAY DIFFRACTION (1.8 Å)