4wop

Nucleotide Triphosphate Promiscuity in Mycobacterium tuberculosis Dethiobiotin Synthetase

spinqualitylabelsall models 4wop, resolution 2.39Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4wop is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CTP, SO4 Activity: Dethiobiotin synthase, with EC number 6.3.3.3 Resources: FirstGlance, OCA, RCSB, PDBsum Function [BIOD_MYCTA] Catalyzes a mechanistically unusual reaction, the ATP-dependent insertion of CO2 between the N7 and N8 nitrogen atoms of 7,8-diaminopelargonic acid (DAPA) to form an ureido ring. Publication Abstract from PubMed Dethiobiotin synthetase (DTBS) plays a crucial role in biotin biosynthesis in microorganisms, fungi, and plants. Due to its importance in bacterial pathogenesis, and the absence of a human homologue, DTBS is a promising target for the development of new antibacterials desperately needed to combat antibiotic resistance. Here we report the first X-ray structure of DTBS from Mycobacterium tuberculosis (MtDTBS) bound to a nucleotide triphosphate (CTP). The nucleoside base is stabilized in its pocket through hydrogen-bonding interactions with the protein backbone, rather than amino acid side chains. This resulted in the unexpected finding that MtDTBS could utilise ATP, CTP, GTP, ITP, TTP, or UTP with similar Km and kcat values, although the enzyme had the highest affinity for CTP in competitive binding and surface plasmon resonance assays. This is in contrast to other DTBS homologues that preferentially bind ATP primarily through hydrogen-bonds between the purine base and the carboxamide side chain of a key asparagine. Mutational analysis performed alongside in silico experiments revealed a gate-keeper role for Asn175 in Escherichia coli DTBS that excludes binding of other nucleotide triphosphates. Here we provide evidence to show that MtDTBS has a broad nucleotide specificity due to the absence of the gate-keeper residue. Nucleotide triphosphate promiscuity in Mycobacterium tuberculosis dethiobiotin synthetase.,Salaemae W, Yap MY, Wegener KL, Booker GW, Wilce MC, Polyak SW Tuberculosis (Edinb). 2015 Mar 6. pii: S1472-9792(15)20712-3. doi:, 10.1016/j.tube.2015.02.046. PMID:25801336 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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