8hd4 | pdb_00008hd4
Full-length crystal structure of mycobacterium tuberculosis FadD23 in complex with AMPC16
Structural highlights
FunctionFAA23_MYCTU Catalyzes the activation of long-chain fatty acids as acyl-adenylates (acyl-AMP), which are then transferred to the multifunctional polyketide synthase (PKS) type III for further chain extension (Probable). Involved in the biosynthesis of sulfolipid 1 (SL-1) (PubMed:17389997, PubMed:17768256).[1] [2] [3] Publication Abstract from PubMedSulfolipid-1 (SL-1) is located in the Mycobacterium tuberculosis (M. tb) cell wall, and is essential for pathogen virulence and intracellular growth. Multiple proteins (e.g., Pks2, FadD23, PapA1, and MmpL8) in the SL-1 synthesis pathway can be treated as drug targets, but, to date, their structures have not been solved. The crystal structures of FadD23 bound to ATP or hexadecanoyl adenylate was determined in this study. We have also investigated long-chain saturated fatty acids as biological substrates of FadD23 through structural, biological, and chemical analyses. The mutation at the active site of FadD23 greatly influences enzymatic activity. Meanwhile, the FadD23 N-terminal domain alone cannot bind palmitic acid without C-terminal domain facilitation since it is almost inactive after removing the C-terminal domain. FadD23 is the first protein in the SL-1 synthesis pathway whose structure has been solved. These results reveal the importance of the C-terminal domain in the catalytic mechanism. The Key Roles of Mycobacterium tuberculosis FadD23 C-terminal Domain in Catalytic Mechanisms.,Yan M, Cao L, Zhao L, Zhou W, Liu X, Zhang W, Rao Z Front Microbiol. 2023 Feb 21;14:1090534. doi: 10.3389/fmicb.2023.1090534. , eCollection 2023. PMID:36896429[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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