3ann | pdb_00003ann

Crystal structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) complexed with quinolin-2-ylmethylphosphonic acid

spinqualitylabelsall models 3ann, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ann is a 2 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: NDP, SYE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DXR_ECOLI Catalyzes the NADP-dependent rearrangement and reduction of 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP).[HAMAP-Rule:MF_00183] Publication Abstract from PubMed Fosmidomycin, a potent inhibitor of 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR), has antibacterial and antimalaria activity. Due to its poor pharmacokinetics, more lipophilic DXR inhibitors are needed. However, the hydrophobic binding site(s) in DXR remains elusive. Here, pyridine/quinoline containing phosphonates are identified to be DXR inhibitors with IC(50) values as low as 840 nM. We also report three DXR:inhibitor structures, revealing a novel binding mode. The indole group of Trp211 is found to move ~4.6 A to open up a mainly hydrophobic pocket, where the pyridine/quinoline rings of the inhibitors are located and have strong pi-pi stacking/charge-transfer interactions with the indole. Docking studies demonstrate our structures could be used to predict the binding modes of other lipophilic DXR inhibitors. Overall, this work shows an important role of Trp211 in inhibitor recognition and provides a structural basis for future drug design and development. Structures of 1-Deoxy-D-Xylulose-5-Phosphate Reductoisomerase/Lipophilic Phosphonate Complexes.,Deng L, Endo K, Kato M, Cheng G, Yajima S, Song Y ACS Med Chem Lett. 2011 Feb 10;2(2):165-170. PMID:21379374 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also DXP reductoisomerase 3D Structures

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