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Crystal Structure of the MoaE-like domain within Rv3323c from Mycobacterium tuberculosis
Structural highlights
FunctionQ6MWY3_MYCTU Converts molybdopterin precursor Z into molybdopterin. This requires the incorporation of two sulfur atoms into precursor Z to generate a dithiolene group. The sulfur is provided by MoaD.[ARBA:ARBA00025448] Publication Abstract from PubMedMolybdoenzymes are essential for the survival and pathogenicity of Mycobacterium tuberculosis and require the molybdenum cofactor (MoCo). The biosynthesis of MoCo involves the molybdopterin (MPT) synthase complex, which is composed of the MoaD and MoaE subunits. The genome of M. tuberculosis encodes three homologs of MoaE: MoaE1, MoaE2, and MoaXE (the latter being a MoaE component of a MoaD-MoaE fusion protein known as MoaX), as well as three MoaD proteins. However, the structural basis for their functional specificity and interaction with MoaD partners remains unclear. We determined the crystal structures of all three MoaE proteins, revealing a conserved alpha/beta hammerhead fold with distinct binding interface features resulting from minor sequence variations. Pull-down assays demonstrate that MoaE2 and MoaXE selectively interact with their cognate MoaD partners, while MoaE1 exhibits promiscuous binding to all MoaD forms. Although the structural plasticity of MoaE1 enables binding to three MoaD forms, it suggests that not all MoaE-MoaD combinations yield functional MPT synthase complexes, as structural rearrangements can lead to enzymatic inactivation. Our findings provide detailed insights into the molecular determinants that govern the assembly and specificity of MPT synthase in M. tuberculosis. Structural comparison of three MoaE proteins in Mycobacterium tuberculosis: Insights into molybdopterin synthase assembly and specificity.,Cho HJ, Yang SH, Lee HS, Kang BS Biochem Biophys Res Commun. 2025 Jul 1;768:151945. doi: , 10.1016/j.bbrc.2025.151945. Epub 2025 May 5. PMID:40345009[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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