EMD-27003
KS-AT domains of mycobacterial Pks13 with inward AT conformation
EMD-27003
Single-particle3.0 Å
Deposition: 17/05/2022
Map released: 15/02/2023
Last modified: 13/11/2024
Sample Organism:
Mycolicibacterium smegmatis MC2 155
Sample: Mycobacterial polyketide synthase 13 KS-AT domains with inward AT conformation
Fitted models: 8cuz (Avg. Q-score: 0.522)
Raw data: EMPIAR-11608
Deposition Authors: Kim SK , Dickinson MS , Finer-Moore JS , Rosenberg OS , Stroud RM
Sample: Mycobacterial polyketide synthase 13 KS-AT domains with inward AT conformation
Fitted models: 8cuz (Avg. Q-score: 0.522)
Raw data: EMPIAR-11608
Deposition Authors: Kim SK , Dickinson MS , Finer-Moore JS , Rosenberg OS , Stroud RM
Structure and dynamics of the essential endogenous mycobacterial polyketide synthase Pks13.
Kim SK ,
Dickinson MS ,
Finer-Moore J,
Guan Z ,
Kaake RM ,
Echeverria I ,
Chen J ,
Pulido EH ,
Sali A ,
Krogan NJ ,
Rosenberg OS ,
Stroud RM
(2023) Nat Struct Mol Biol , 30 , 296 - 308
(2023) Nat Struct Mol Biol , 30 , 296 - 308
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.
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.