UDP-3-O-acyl-N-acetylglucosamine deacetylase

Function UDP-3-O-acyl-N-acetylglucosamine deacetylase (LpxC) is a Zn-dependent protein which participates in the biosynthesis of lipid A. Lipid A anchors lipopolysaccharides into the membrane of Gram negative bacteria. LpxC catalyzes the conversion of UDP-3-O-[(3R)-3-hydroxymyristoyl]-N-acetylglucosamine to UDP-3-O-[(3R)-3-hydroxymyristoyl]-N-glucosamine. (PDB code 4mdt). . . Water molecules are shown as red spheres. . . . . Para-(benzoyl)-phenylalanine as a potential inhibitor against LpxC of Leptospira spp.: Homology modeling, docking and molecular dynamics study Leptospira interrogans, a Gram-negative bacterial pathogen is the main cause of human leptospirosis. Lipid A is a highly immunoreactive endotoxic center of lipopolysaccharide (LPS) that anchors LPS into the outer membrane of Leptospira. Discovery of compounds inhibiting lipid-A biosynthetic pathway would be promising for dissolving the structural integrity of membrane leading to cell lysis and death of Leptospira. , a unique enzyme of lipid-A biosynthetic pathway was identified as common drug target of Leptospira. Herein, homology modeling, docking, and molecular dynamics (MD) simulations were employed to discover potential inhibitors of LpxC. A was constructed in Modeller 9v8. between active site of target and template (LpxC from Pseudomonas aeruginosa, PDB entry 2ves) in the presence of BB-78485. The color code representations as deep pink: target; green: template; cyan: BB-78485 in complex with target; and darkmagenta: BB-78485 in complex with template. Zn ion represented as sphere. A data-set of BB-78485 structural analogs were docked with LpxC in Maestro v9.2 virtual screening workflow, which implements three stage Glide docking protocol. Twelve lead molecules with better XP Gscore compared to BB-78485 were proposed as potential inhibitors of LpxC. Para-(benzoyl)-phenylalanine – that showed lowest XP Gscore (−10.35 kcal/mol) – was predicted to have best binding affinity towards LpxC. MD simulations were performed for LpxC and para-(benzoyl)-phenylalanine docking complex in Desmond v3.0. Trajectory analysis showed the docking complex and inter-molecular interactions was stable throughout the entire production part of MD simulations. The results indicate para-(benzoyl)-phenylalanine as a potent drug molecule against leptospirosis. 3D Structures of UDP-3-O-acyl-N-acetylglucosamine deacetylase UDP-3-O-acyl-N-acetylglucosamine deacetylase 3D structures Updated on 04-May-2025 {{#tree:id=OrganizedByTopic|openlevels=0| UDP-3-O-acyl-N-acetylglucosamine deacetylase complexes 1yh8 – AaLpxC (mutant) + Zn + palmitate – Aquifex aeolicus 1p42 – AaLpxC (mutant) + Zn + myristate 1yhc – AaLpxC (mutant) + Zn + palmitate + cacodylate 2j65 – AaLpxC (mutant) + Zn + myristate + UDP 2ier – AaLpxC (mutant) + Zn + palmitate + UDP 2ies – AaLpxC (mutant) + Zn + palmitate + pyrophosphate 4mdt – EcLpxC + Zn + UDP-(3-O-(R-3-hydroxymyristoyl))-glucosamine – Escherichia coli UDP-3-O-acyl-N-acetylglucosamine deacetylase complex with inhibitor 1xxe – AaLpxC + Zn + inhibitor - NMR 3p76, 5dro, 5drp, 5drq, 5drr, 4u3b, 4u3d, 6ih0 – AaLpxC + Zn + inhibitor 2go4, 3p3c, 5u86 – AaLpxC (mutant) + Zn + inhibitor 2go3 – AaLpxC (mutant) + Zn + myristate + cacodylate + imidazole 2o3z – AaLpxC (mutant) + Zn + benzoate derivative 2jt2 – AaLpxC (mutant) + Zn + antibiotic - NMR 4oze – AaLpxC + Zn + native product 4j3d, 4fw3, 4fw4, 4fw5, 4fw6, 4fw7, 5u3b, 5u39, 5upg, 5vwm, 6mae, 6cax, 6c9c, 6dui, 6e54, 6mo4, 6mo5, 6mod, 6moo, 6i46, 6u47, 6i48, 6i49, 6i4a, 7cic, 7ci4, 7ci5, 7ci6, 7ci7, 7ci8, 7ci9, 7cia, 7cib, 7cid, 7cie, 7k99, 7k9a – PaLpxC + Zn + inhibitor – Pseudomonas aeruginosa 2ves – PaLpxC (mutant) + Zn + inhibitor - NMR 3p3e, 3u1y, 3uhm, 4lcf, 4lcg, 4lch, 4okg, 5n8c – PaLpxC (mutant) + Zn + inhibitor 3nzk – LpxC + Zn + inhibitor – Yersinia enterocolitica 3p3g, 3ps1, 3ps2, 3ps3, 4mqy, 4is9, 4isa – EcLpxC + Zn + inhibitor }}

spinqualitylabelsall models Structure of E. coli UDP-3-O-acyl-N-acetylglucosamine deacetylase complex with Zn+2 ion (grey) and UDP-(3-O-(R-3-hydroxymyristoyl))-glucosamine (PDB code 4mdt). Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image