3qas

Structure of Undecaprenyl Diphosphate synthaseStructure of Undecaprenyl Diphosphate synthase

Structural highlights 3qas is a 2 chain structure with sequence from Ecoli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: uppS, ispU, rth, yaeS (ECOLI) Activity: Ditrans,polycis-undecaprenyl-diphosphate synthase ((2E,6E)-farnesyl- diphosphate specific), with EC number 2.5.1.31 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [UPPS_ECOLI] Generates ditrans,octacis-undecaprenyl pyrophosphate (UPP) from isopentenyl pyrophosphate (IPP) and farnesyl diphosphate (FPP). UPP is the precursor of glycosyl carrier lipid in the biosynthesis of bacterial cell wall polysaccharide components such as peptidoglycan and lipopolysaccharide. Publication Abstract from PubMed Undecaprenyl pyrophosphate synthase (UPPS) is a cis-prenyltransferase enzyme, which is required for cell-wall biosynthesis in bacteria. UPPS is an attractive target for anti-microbial therapy. We performed long molecular dynamics (MD) simulations and docking studies on UPPS to investigate its dynamic behavior and the influence of protein flexibility on the design of UPPS inhibitors. We also describe the first x-ray crystallographic structure of E. coli apo-UPPS. The MD simulations indicate that UPPS is a highly flexible protein, with mobile binding pockets in the active site. By carrying out docking studies with experimentally validated UPPS inhibitors using high and low populated conformational states extracted from the MD simulations, we show that structurally dissimilar compounds can bind preferentially to different and rarely sampled conformational states. By performing structural analyses on the newly obtained apo-UPPS and other crystal structures previously published, we show that the changes observed during the MD simulation are very similar to those seen in the crystal structures obtained in the presence or absense of ligands. We believe that this is the first time that a rare "expanded pocket" state, a key to drug design and verified by crystallography, has been extracted from an MD simulation. Applying Molecular Dynamics Simulations to Identify Rarely Sampled Ligand-bound Conformational States of Undecaprenyl Pyrophosphate Synthase, an Antibacterial Target.,Sinko W, de Oliveira C, Williams S, Van Wynsberghe A, Durrant JD, Cao R, Oldfield E, Andrew McCammon J Chem Biol Drug Des. 2011 Feb 5. doi: 10.1111/j.1747-0285.2011.01101.x. PMID:21294851 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Undecaprenyl pyrophosphate synthase

spinqualitylabelsall models 3qas, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image