6bug

Crystal structure of a membrane protein, crystal form I

spinqualitylabelsall models 6bug, resolution 3.27Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6bug is a 7 chain structure with sequence from Streptococcus thermophilus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.27Å Ligands: SEP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DLTC_STRT2 Carrier protein involved in the D-alanylation of lipoteichoic acid (LTA). The loading of thioester-linked D-alanine onto DltC is catalyzed by D-alanine--D-alanyl carrier protein ligase DltA. The DltC-carried D-alanyl group is further transferred to cell membrane phosphatidylglycerol (PG) by forming an ester bond, probably catalyzed by DltD. D-alanylation of LTA plays an important role in modulating the properties of the cell wall in Gram-positive bacteria, influencing the net charge of the cell wall.[HAMAP-Rule:MF_00565] Publication Abstract from PubMed Membrane-bound O-acyltransferases (MBOATs) are a superfamily of integral transmembrane enzymes that are found in all kingdoms of life(1). In bacteria, MBOATs modify protective cell-surface polymers. In vertebrates, some MBOAT enzymes-such as acyl-coenzyme A:cholesterol acyltransferase and diacylglycerol acyltransferase 1-are responsible for lipid biosynthesis or phospholipid remodelling(2,3). Other MBOATs, including porcupine, hedgehog acyltransferase and ghrelin acyltransferase, catalyse essential lipid modifications of secreted proteins such as Wnt, hedgehog and ghrelin, respectively(4-10). Although many MBOAT proteins are important drug targets, little is known about their molecular architecture and functional mechanisms. Here we present crystal structures of DltB, an MBOAT responsible for the D-alanylation of cell-wall teichoic acid in Gram-positive bacteria(11-16), both alone and in complex with the D-alanyl donor protein DltC. DltB contains a ring of 11 peripheral transmembrane helices, which shield a highly conserved extracellular structural funnel extending into the middle of the lipid bilayer. The conserved catalytic histidine residue is located at the bottom of this funnel and is connected to the intracellular DltC through a narrow tunnel. Mutation of either the catalytic histidine or the DltC-binding site of DltB abolishes the D-alanylation of lipoteichoic acid and sensitizes the Gram-positive bacterium Bacillus subtilis to cell-wall stress, which suggests cross-membrane catalysis involving the tunnel. Structure-guided sequence comparison among DltB and vertebrate MBOATs reveals a conserved structural core and suggests that MBOATs from different organisms have similar catalytic mechanisms. Our structures provide a template for understanding structure-function relationships in MBOATs and for developing therapeutic MBOAT inhibitors. Crystal structure of a membrane-bound O-acyltransferase.,Ma D, Wang Z, Merrikh CN, Lang KS, Lu P, Li X, Merrikh H, Rao Z, Xu W Nature. 2018 Oct;562(7726):286-290. doi: 10.1038/s41586-018-0568-2. Epub 2018 Oct, 3. PMID:30283133 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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