<i>Escherichia</i><i>coli</i> versus <i>Pseudomonas aeruginosa</i> Deacetylase LpxC Inhibitors Selectivity:  Surface and Cavity-Depth-Based Analysis KadamRameshwar U. ShivangeAmol V. RoyNilanjan 2007 Although <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i> LpxC share sequence and functional similarity, <i>E. coli</i> LpxC inhibitiors are ineffective against <i>P. aeruginosa</i> LpxC. It was earlier speculated that inactivity of the inhibitors is due to intrinsic resistance possibly mediated by efflux pumps. However, a recent study has documented that the inactivity is due to failure of inhibitor(s) to inhibit the enzyme rather then intrinsic resistance. In this study, we carried out a surface and cavity-depth-based analysis on homology models of <i>E. coli</i> and <i>P. aeruginosa</i> LpxC to get some new insights into the ligand-binding features of these enzymes. The surface analysis of the <i>P. aeruginosa</i> LpxC model suggested that the LpxC catalytic domain (where inhibitors are supposed to bind) has several minor but potentially important structural differences as compared to <i>E. coli</i> LpxC. Molecular docking studies which could distinguish between the reported receptor affinities of the inhibitors additionally helped in the identification of key binding-site residues and interactions. These differences can be exploited for designing broad-spectrum LpxC inhibitors against this target.