4utt

Structural characterisation of NanE, ManNac6P C2 epimerase, from Clostridium perfingens

spinqualitylabelsall models 4utt, resolution 1.71Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4utt is a 4 chain structure with sequence from Clope. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACT, CL Related: 4utu, 4utw Activity: N-acylglucosamine-6-phosphate 2-epimerase, with EC number 5.1.3.9 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [NANE_CLOP1] Converts N-acetylmannosamine-6-phosphate (ManNAc-6-P) to N-acetylglucosamine-6-phosphate (GlcNAc-6-P). Publication Abstract from PubMed Pathogenic bacteria are endowed with an arsenal of specialized enzymes to convert nutrient compounds from their cell hosts. The essential N-acetylmannosamine-6-phosphate 2-epimerase (NanE) belongs to a convergent glycolytic pathway for utilization of the three amino sugars, GlcNAc, ManNAc and sialic acid. The crystal structure of ligand-free NanE from Clostridium perfringens reveals a modified TIM (beta/alpha)8 barrel in which a stable dimer is formed by exchanging the C-terminal helix. By retaining catalytic activity in the crystalline state, the structure of the enzyme bound to the GlcNAc-6P product identifies the topology of the active site pocket and points to invariant residues Lys66 as a putative single catalyst, supported by the structure of the (catalytically inactive) Lys66Ala mutant in complex with substrate ManNAc-6P. 1H-NMR-based time course assays of native NanE and mutated variants demonstrate the essential role of Lys66 for the epimerization reaction with participation of neighboring Arg43, Asp126 and Glu180 residues. These findings unveil a one-base catalytic mechanism of C2 deprotonation/reprotonation via an enolate intermediate and provide the structural basis for the development of new antimicrobial agents against this family of bacterial 2-epimerases. Structural and functional characterization of the Clostridium perfringens N-acetylmannosamine-6-phosphate 2-epimerase essential for the sialic acid salvage pathway.,Pelissier MC, Sebban-Kreuzer C, Guerlesquin F, Brannigan JA, Bourne Y, Vincent F J Biol Chem. 2014 Oct 15. pii: jbc.M114.604272. PMID:25320079 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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