Structural highlights
FunctionFAA32_MYCTU Catalyzes the activation of long-chain fatty acids as acyl-adenylates (acyl-AMP), which are then transferred to the multifunctional polyketide synthase (PKS) for further chain extension.[1] Publication Abstract from PubMedMycolic acids are indispensible lipids of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), and contribute to the distinctive architecture and impermeability of the mycobacterial cell envelope. FadD32 plays a pivotal role in mycolic acid biosynthesis by functionally linking fatty acid synthase (FAS) and polyketide synthase (PKS) biosynthetic pathways. FadD32, a fatty acyl-AMP ligase (FAAL), represents one of the best genetically and chemically validated new TB drug targets. We have determined the three-dimensional crystal structure of Mtb FadD32 in complex with a ligand specifically designed to stabilize the catalytically active adenylate-conformation, which provides a foundation for structure-based drug design efforts against this essential protein. The structure also captures the unique interactions of a FAAL-specific insertion sequence and provides insight into the specificity and mechanism of fatty acid transfer. Structure of the Essential Mtb FadD32 Enzyme: A Promising Drug Target for Treating Tuberculosis.,Kuhn ML, Alexander E, Minasov G, Page HJ, Warwrzak Z, Shuvalova L, Flores KJ, Wilson DJ, Shi C, Aldrich CC, Anderson WF ACS Infect Dis. 2016 Aug 12;2(8):579-591. Epub 2016 Jul 1. PMID:27547819[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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