4knw

The crystal structure of human HDHD4 IN COMPLEX WITH MAGNESIUM AND THE PHOSPHATE MIMETIC VANADATE

spinqualitylabelsall models 4knw, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4knw is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.699Å Ligands: MG, VO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NANP_HUMAN Publication Abstract from PubMed The design, synthesis and characterization of a phosphonate inhibitor of N-acetylneuraminate-9-phosphate phosphatase (HDHD4) is described. Compound 3, where the substrate C-9 oxygen was replaced with a nonlabile CH2 group, inhibits HDHD4 with a binding affinity (IC50 11muM) in the range of the native substrate Neu5Ac-9-P (compound 1, Km 47muM). Combined SAR, modeling and NMR studies are consistent with the phosphonate group in inhibitor 3 forming a stable complex with native Mg(2+). In addition to this key interaction, the C-1 carboxylate of the sugar interacts with a cluster of basic residues, K141, R104 and R72. Comparative NMR studies of compounds 3 and 1 with Ca(2+) and Mg(2+) are indicative of a highly dynamic process in the active site for the HDHD4/Mg(2+)/3 complex. Possible explanations for this observation are discussed. Design, synthesis, functional and structural characterization of an inhibitor of N-acetylneuraminate-9-phosphate phosphatase: Observation of extensive dynamics in an enzyme/inhibitor complex.,Kim SH, Constantine KL, Duke GJ, Goldfarb V, Hunt JT, Johnson S, Kish K, Klei HE, McDonnell PA, Metzler WJ, Mueller L, Poss MA, Fairchild CR, Bhide RS Bioorg Med Chem Lett. 2013 Jul 15;23(14):4107-11. doi:, 10.1016/j.bmcl.2013.05.052. Epub 2013 May 23. PMID:23747226 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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