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-Structure paper
| Title | Visualizing acyl carrier protein interactions within a crosslinked type I polyketide synthase. |
|---|---|
| Journal, issue, pages | Nat Commun, Vol. 16, Issue 1, Page 7798, Year 2025 |
| Publish date | Aug 21, 2025 |
Authors | Ziran Jiang / Graham W Heberlig / Jeffrey A Chen / Jennifer Huynh / James J La Clair / Michael D Burkart / ![]() |
| PubMed Abstract | Using a combination of dual covalent crosslinking and cryo-EM analyses, we elucidate the structure of mycocerosic acid synthase from Mycobacterium tuberculosis trapped in two distinct catalytic ...Using a combination of dual covalent crosslinking and cryo-EM analyses, we elucidate the structure of mycocerosic acid synthase from Mycobacterium tuberculosis trapped in two distinct catalytic states during its iterative cycle. These structures reveal domain architecture of the acyl carrier protein mediating condensation and dehydration through dual site-selective crosslinking of the acyl carrier protein with the ketosynthase and dehydratase domains. Map density was sufficient to visualize full domain architecture with active site-bound probes and elucidate key interactions of four distinct crosslinked species. Here, iterative vectorial polyketide biosynthesis arises through an overall twisting and tilting architecture, enabling positioning and entry of the cognate substrate at each enzymatic domain. These structures present valuable details for future therapeutic design against mycocerosic acid biosynthesis in M. tuberculosis. |
External links | Nat Commun / PubMed:40841798 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 3.22 - 6.15 Å |
| Structure data | EMDB-46504, PDB-9d2y: EMDB-46505, PDB-9d2z: EMDB-46506, PDB-9d30: ![]() EMDB-46507: Cryo-EM structure of mycocerosic acid synthase with KS-ACP' crosslink and DH-ACP crosslink using C16 alpha-bromoamide. Complex D |
| Chemicals | ![]() PDB-1by8: ![]() ChemComp-MU4: |
| Source |
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Keywords | BIOSYNTHETIC PROTEIN / FAS / polyketide / crosslinked / ketosynthase / dehydratase |
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