6dft

Trypanosoma brucei deoxyhypusine synthaseTrypanosoma brucei deoxyhypusine synthase

Structural highlights 6dft is a 12 chain structure with sequence from Trypanosoma brucei. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.5Å Ligands: , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DHYSC_TRYB2 In association with the non-catalytic regulatory subunit DHSp, catalyzes the NAD-dependent oxidative cleavage of spermidine and the subsequent transfer of the butylamine moiety of spermidine to the epsilon-amino group of a specific lysine residue of the eIF5A precursor protein to form the intermediate deoxyhypusine residue. Regulates protein levels of its regulatory subunit DHSp. Required for cell growth and survival. Publication Abstract from PubMed Trypanosoma brucei is a neglected tropical disease endemic to Africa. The polyamine spermidine is essential for post-translational hypusine modification of eukaryotic initiation factor 5A (eIF5A), which is catalyzed by deoxyhypusine synthase (TbDHS). In trypanosomatids, deoxyhypusine synthase (DHS) activity is dependent on heterotetramer formation between two paralogs, DHSc and DHSp, both with minimal activity on their own due to missing catalytic residues. We determined the X-ray structure of TbDHS showing a single functional shared active site is formed at the DHSc/DHSp heterodimer interface, with deficiencies in one subunit complemented by the other. Each heterodimer contains two NAD(+) binding sites, one housed in the functional catalytic site and the second bound in a remnant dead site that lacks key catalytic residues. Functional analysis of these sites by site-directed mutagenesis identified long-range contributions to the catalytic site from the dead site. Differences between trypanosomatid and human DHS that could be exploited for drug discovery were identified. Trypanosomatid Deoxyhypusine Synthase Activity Is Dependent on Shared Active-Site Complementation between Pseudoenzyme Paralogs.,Afanador GA, Tomchick DR, Phillips MA Structure. 2018 Nov 6;26(11):1499-1512.e5. doi: 10.1016/j.str.2018.07.012. Epub, 2018 Sep 6. PMID:30197036 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Deoxyhypusine synthase

spinqualitylabelsall models 6dft, resolution 3.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image