6xp4 | pdb_00006xp4

Nucleoside Diphosphate Kinase from Aspergillus fumgiatus Af293

spinqualitylabelsall models 6xp4, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6xp4 is a 6 chain structure with sequence from Aspergillus fumigatus Af293. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NDK_ASPFU Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate. Publication Abstract from PubMed Aspergillus fumigatus infections are rising at a disconcerting rate in tandem with antifungal resistance rates. Efforts to develop novel antifungals has been hindered by the limited knowledge of fundamental biological and structural mechanisms of A. fumigatus propagation. Biosynthesis of NTPs, the building blocks of DNA and RNA, is catalysed by NDK. An essential enzyme in A. fumigatus, NDK poses as an attractive target for novel antifungals. NDK exhibits broad substrate specificity across species, using both purines and pyrimidines, but the selectivity of such nucleosides in A. fumigatus NDK is unknown, impeding structure-guided inhibitor design. Structures of NDK in unbound- and NDP-bound states were solved and NDK activity was assessed in the presence of various NTP substrates. We present the first instance of a unique substrate binding mode adopted by CDP and TDP specific to A. fumigatus NDK that illuminates the structural determinants of selectivity. Analysis of the oligomeric state reveals that A. fumigatus NDK adopts a hexameric assembly in both unbound- and NDP-bound states, contrary to previous reports suggesting it is tetrameric. Kinetic analysis revealed that ATP exhibited the greatest turnover rate (321 +/- 33.0 s(-1) ), specificity constant (626 +/- 110.0 mM(-1) s(-1) ) and binding free energy change (-37.0 +/- 3.5 kcal/mol). Comparatively, cytidine nucleosides displayed the slowest turnover rate (53.1 +/- 3.7 s(-1) ) and lowest specificity constant (40.2 +/- 4.4 mM(-1) s(-1) ). We conclude that NDK exhibits nucleoside selectivity whereby adenine nucleosides are used preferentially compared to cytidine nucleosides, and these insights can be exploited to guide drug design. Nucleoside selectivity of Aspergillus fumigatus nucleoside-diphosphate kinase.,Nguyen S, Jovcevski B, Pukala TL, Bruning JB FEBS J. 2020 Oct 21. doi: 10.1111/febs.15607. PMID:33089641 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Nucleoside diphosphate kinase 3D structures

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