6ofd

The crystal structure of octadecyloxy(naphthalen-1-yl)methylphosphonic acid in complex with red kidney bean purple acid phosphatase

spinqualitylabelsall models 6ofd, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ofd is a 4 chain structure with sequence from Phaseolus vulgaris. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.2Å Ligands: BMA, CL, EDO, FE, FUC, GOL, MAN, MF1, NA, NAG, PGE, SO4, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PPAF_PHAVU Publication Abstract from PubMed Purple acid phosphatases (PAPs) are binuclear hydrolases that catalyze the hydrolysis of phosphorylated substrates under acidic to neutral conditions. Elevated serum concentrations of PAP are observed in patients suffering from osteoporosis, identifying this enzyme as a potential target for the development of novel therapeutic agents to treat this disease. alpha-Alkoxy-substituted naphthylmethylphosphonic acid derivatives have been identified previously as molecules that bind with high affinity to PAPs, and docking studies suggest that longer alkyl chains may increase the binding affinities of such compounds. Here, we synthesized several derivatives and tested their inhibitory effect against pig and red kidney bean PAPs. The most potent inhibitor within this series is the octadecyl derivative, which has a Ki value of approximately 200nM. Crystal structures of the dodecyl and octadecyl derivatives bound to red kidney bean PAP show that the length of the alkyl chain influences the ability of the phosphonate group to interact directly with the bimetallic center. These structures represent the first examples of potent inhibitors bound to a PAP that have drug-like properties. This study provides a starting point for the development of much needed new treatments for osteoporosis. Synthesis, evaluation and structural investigations of potent purple acid phosphatase inhibitors as drug leads for osteoporosis.,Feder D, Kan MW, Hussein WM, Guddat LW, Schenk G, McGeary RP Eur J Med Chem. 2019 Nov 15;182:111611. doi: 10.1016/j.ejmech.2019.111611. Epub, 2019 Aug 13. PMID:31445230 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acid phosphatase 3D structures

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