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Structure and dynamics of the essential endogenous mycobacterial polyketide synthase Pks13.

Publication ,  Journal Article
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
Published in: Nat Struct Mol Biol
March 2023

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.

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Published In

Nat Struct Mol Biol

DOI

EISSN

1545-9985

Publication Date

March 2023

Volume

30

Issue

3

Start / End Page

296 / 308

Location

United States

Related Subject Headings

  • Polyketide Synthases
  • Mycolic Acids
  • Mycobacterium tuberculosis
  • Fatty Acids
  • Developmental Biology
  • Biophysics
  • 11 Medical and Health Sciences
  • 06 Biological Sciences
  • 03 Chemical Sciences
 

Citation

APA
Chicago
ICMJE
MLA
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Kim, S. K., Dickinson, M. S., Finer-Moore, J., Guan, Z., Kaake, R. M., Echeverria, I., … Stroud, R. M. (2023). Structure and dynamics of the essential endogenous mycobacterial polyketide synthase Pks13. Nat Struct Mol Biol, 30(3), 296–308. https://doi.org/10.1038/s41594-022-00918-0
Kim, Sun Kyung, Miles Sasha Dickinson, Janet Finer-Moore, Ziqiang Guan, Robyn M. Kaake, Ignacia Echeverria, Jen Chen, et al. “Structure and dynamics of the essential endogenous mycobacterial polyketide synthase Pks13.Nat Struct Mol Biol 30, no. 3 (March 2023): 296–308. https://doi.org/10.1038/s41594-022-00918-0.
Kim SK, Dickinson MS, Finer-Moore J, Guan Z, Kaake RM, Echeverria I, et al. Structure and dynamics of the essential endogenous mycobacterial polyketide synthase Pks13. Nat Struct Mol Biol. 2023 Mar;30(3):296–308.
Kim, Sun Kyung, et al. “Structure and dynamics of the essential endogenous mycobacterial polyketide synthase Pks13.Nat Struct Mol Biol, vol. 30, no. 3, Mar. 2023, pp. 296–308. Pubmed, doi:10.1038/s41594-022-00918-0.
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. Structure and dynamics of the essential endogenous mycobacterial polyketide synthase Pks13. Nat Struct Mol Biol. 2023 Mar;30(3):296–308.

Published In

Nat Struct Mol Biol

DOI

EISSN

1545-9985

Publication Date

March 2023

Volume

30

Issue

3

Start / End Page

296 / 308

Location

United States

Related Subject Headings

  • Polyketide Synthases
  • Mycolic Acids
  • Mycobacterium tuberculosis
  • Fatty Acids
  • Developmental Biology
  • Biophysics
  • 11 Medical and Health Sciences
  • 06 Biological Sciences
  • 03 Chemical Sciences