8CUY

ACP1-KS-AT domains of mycobacterial Pks13

Summary for 8CUY

• Entry DOI: 10.2210/pdb8cuy/pdb
• Related: 7UK4 8CUZ 8CV0 8CV1
• EMDB information: 26574 27002 27003 27004 27005
• Descriptor: Polyketide synthase PKS13, UNKNOWN LIGAND, 4'-PHOSPHOPANTETHEINE, ... (4 entities in total)
• Functional Keywords: mycolic acid synthesis, acyl carrier protein, ketosynthase, acyltransferase, multi-domain assembly, biosynthetic protein
• Biological source: Mycolicibacterium smegmatis MC2 155
• Total number of polymer chains: 2
• Total formula weight: 390944.87

Authors

Kim, S.K.,Dickinson, M.S.,Finer-Moore, J.S.,Rosenberg, O.S.,Stroud, R.M. (deposition date: 2022-05-17, release date: 2023-02-15, Last modification date: 2023-03-29)

Primary citation

Kim, S.K.,Dickinson, M.S.,Finer-Moore, J.,Guan, Z.,Kaake, R.M.,Echeverria, I.,Chen, J.,Pulido, E.H.,Sali, A.,Krogan, N.J.,Rosenberg, O.S.,Stroud, R.M.
Structure and dynamics of the essential endogenous mycobacterial polyketide synthase Pks13.
Nat.Struct.Mol.Biol., 30:296-308, 2023

PubMed Abstract: The mycolic acid layer of the Mycobacterium tuberculosis cell wall is essential for viability and virulence, and the enzymes responsible for its synthesis are targets for antimycobacterial drug development. Polyketide synthase 13 (Pks13) is a module encoding several enzymatic and transport functions that carries out the condensation of two different long-chain fatty acids to produce mycolic acids. We determined structures by cryogenic-electron microscopy of dimeric multi-enzyme Pks13 purified from mycobacteria under normal growth conditions, captured with native substrates. Structures define the ketosynthase (KS), linker and acyl transferase (AT) domains at 1.8 Å resolution and two alternative locations of the N-terminal acyl carrier protein. These structures suggest intermediate states on the pathway for substrate delivery to the KS domain. Other domains, visible at lower resolution, are flexible relative to the KS-AT core. The chemical structures of three bound endogenous long-chain fatty acid substrates were determined by electrospray ionization mass spectrometry.

PubMed: 36782050
DOI: 10.1038/s41594-022-00918-0

Experimental method

ELECTRON MICROSCOPY (2.4 Å)