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bioRxiv · 10.1101/2025.11.15.688623

Architecture of an asymmetric mycobacterial short chain/long chain acyl-CoA carboxylase

Mullapudi, E.·Thai, H. M.·de Carvalho, L.·Wilmanns, M.
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Abstract

Endogenous extraction has revealed a mycobacterial hybrid acyl-CoA carboxylase (ACCase) complex exhibiting distinct long-chain (LC) and short-chain (LC) acyl-CoA carboxyl transferase (CT) activities. The presence of two different CT subunits (AccD4, AccD5) is triggered by a unique AccE5 dimer. AccE5 also generates a flexible biotin carboxylase (BC) / CT arrangement through a 9-stranded {beta}-barrel, which rotates the entire BC assembly by [~]90{degrees} in the presence of acyl-CoA substrates. These data demonstrate that asymmetric, multi-substrate ACCases differ fundamentally from symmetric, single-substrate ACCases.

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Mullapudi, E., Thai, H. M., de Carvalho, L., Wilmanns, M.. 2025-11-15. Architecture of an asymmetric mycobacterial short chain/long chain acyl-CoA carboxylase. https://doi.org/10.1101/2025.11.15.688623

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