4azv

Co-crystal structure of WbdD and kinase inhibitor GW435821x.

spinqualitylabelsall models 4azv, resolution 3.29Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4azv is a 1 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.291Å Ligands: CL, SAM, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function WBDD2_ECOLX Regulates the length of the LPS O-antigen polysaccharide chain. Stops the polymerization of the chain by phosphorylating and then methylating the phosphate on the terminal sugar. This terminal modification is essential for export of the O-antigen across the inner membrane. WbdD is also required for correct localization of the WbdA mannosyltransferase.[UniProtKB:J7I4B7] Publication Abstract from PubMed The Escherichia coli serotype O9a O-antigen polysaccharide (O-PS) is a model for glycan biosynthesis and export by the ATP-binding cassette transporter-dependent pathway. The polymannose O9a O-PS is synthesized as a polyprenol-linked glycan by mannosyltransferase enzymes located at the cytoplasmic membrane. The chain length of the O9a O-PS is tightly regulated by the WbdD enzyme. WbdD first phosphorylates the terminal non-reducing mannose of the O-PS and then methylates the phosphate, stopping polymerization. The 2.2 A resolution structure of WbdD reveals a bacterial methyltransferase domain joined to a eukaryotic kinase domain. The kinase domain is again fused to an extended C-terminal coiled-coil domain reminiscent of eukaryotic DMPK (Myotonic Dystrophy Protein Kinase) family kinases such as Rho-associated protein kinase (ROCK). WbdD phosphorylates 2-alpha-D-mannosyl-D-mannose (2alpha-MB), a short mimic of the O9a polymer. Mutagenesis identifies those residues important in catalysis and substrate recognition and the in vivo phenotypes of these mutants is used to dissect the termination reaction. We have determined the structures of co-complexes of WbdD with two known eukaryotic protein kinase inhibitors. Although these are potent inhibitors in vitro, they do not show any in vivo activity. The structures reveal new insight into O-PS chain-length regulation in this important model system. Structure of WbdD; a bifunctional kinase and methyltransferase that regulates the chain length of the O antigen in Escherichia coli O9a.,Hagelueken G, Huang H, Clarke BR, Lebl T, Whitfield C, Naismith JH Mol Microbiol. 2012 Sep 13. doi: 10.1111/mmi.12014. PMID:22970759 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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