| http://purl.uniprot.org/citations/18422345 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18422345 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18422345 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Citation |
| http://purl.uniprot.org/citations/18422345 | http://www.w3.org/2000/01/rdf-schema#comment | "LpxD catalyzes the third step of lipid A biosynthesis, the (R)-3-hydroxymyristoyl-acyl carrier protein ( R-3-OHC14-ACP)-dependent N-acylation of UDP-3-O-[(R)-3-hydroxymyristoyl]-alpha-D-glucosamine [UDP-3-O-(R-3-OHC14)-GlcN]. We have now overexpressed and purified Escherichia coli LpxD to homogeneity. Steady-state kinetics suggest a compulsory ordered mechanism in which R-3-OHC14-ACP binds prior to UDP-3-O-(R-3-OHC14)-GlcN. The product, UDP-2,3-diacylglucosamine, dissociates prior to ACP; the latter is a competitive inhibitor against R-3-OHC14-ACP and a noncompetitive inhibitor against UDP-3-O-(R-3-OHC14)-GlcN. UDP-2-N-[(R)-3-Hydroxymyristoyl]-alpha-D-glucosamine, obtained by mild base hydrolysis of UDP-2,3-diacylglucosamine, is a noncompetitive inhibitor against both substrates. Synthetic (R)-3-hydroxylauroyl-methylphosphopantetheine is an uncompetitive inhibitor against R-3-OHC14-ACP and a competitive inhibitor against UDP-3-O-(R-3-OHC14)-GlcN, but (R)-3-hydroxylauroyl-methylphosphopantetheine is also a very poor substrate. A compulsory ordered mechanism is consistent with the fact that R-3-OHC14-ACP has a high binding affinity for free LpxD whereas UDP-3-O-(R-3-OHC14)-GlcN does not. Divalent cations inhibit R-3-OHC14-ACP-dependent acylation but not (R)-3-hydroxylauroyl-methylphosphopantetheine-dependent acylation, indicating that the acidic recognition helix of R-3-OHC14-ACP contributes to binding. The F41A mutation increases the K(M) for UDP-3-O-(R-3-OHC14)-GlcN 30-fold, consistent with aromatic stacking of the corresponding F43 side chain against the uracil moiety of bound UDP-GlcNAc in the X-ray structure of Chlamydia trachomatis LpxD. Mutagenesis implicates E. coli H239 but excludes H276 as the catalytic base, and neither residue is likely to stabilize the oxyanion intermediate."xsd:string |
| http://purl.uniprot.org/citations/18422345 | http://purl.org/dc/terms/identifier | "doi:10.1021/bi800240r"xsd:string |
| http://purl.uniprot.org/citations/18422345 | http://purl.org/dc/terms/identifier | "doi:10.1021/bi800240r"xsd:string |
| http://purl.uniprot.org/citations/18422345 | http://purl.org/dc/terms/identifier | "doi:10.1021/bi800240r"xsd:string |
| http://purl.uniprot.org/citations/18422345 | http://purl.uniprot.org/core/author | "Raetz C.R."xsd:string |
| http://purl.uniprot.org/citations/18422345 | http://purl.uniprot.org/core/author | "Raetz C.R."xsd:string |
| http://purl.uniprot.org/citations/18422345 | http://purl.uniprot.org/core/author | "Bartling C.M."xsd:string |
| http://purl.uniprot.org/citations/18422345 | http://purl.uniprot.org/core/author | "Bartling C.M."xsd:string |
| http://purl.uniprot.org/citations/18422345 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18422345 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18422345 | http://purl.uniprot.org/core/name | "Biochemistry"xsd:string |
| http://purl.uniprot.org/citations/18422345 | http://purl.uniprot.org/core/name | "Biochemistry"xsd:string |
| http://purl.uniprot.org/citations/18422345 | http://purl.uniprot.org/core/pages | "5290-5302"xsd:string |
| http://purl.uniprot.org/citations/18422345 | http://purl.uniprot.org/core/pages | "5290-5302"xsd:string |
| http://purl.uniprot.org/citations/18422345 | http://purl.uniprot.org/core/title | "Steady-state kinetics and mechanism of LpxD, the N-acyltransferase of lipid A biosynthesis."xsd:string |
| http://purl.uniprot.org/citations/18422345 | http://purl.uniprot.org/core/title | "Steady-state kinetics and mechanism of LpxD, the N-acyltransferase of lipid A biosynthesis."xsd:string |
| http://purl.uniprot.org/citations/18422345 | http://purl.uniprot.org/core/volume | "47"xsd:string |
| http://purl.uniprot.org/citations/18422345 | http://purl.uniprot.org/core/volume | "47"xsd:string |
| http://purl.uniprot.org/citations/18422345 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/18422345 |
| http://purl.uniprot.org/citations/18422345 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/18422345 |
| http://purl.uniprot.org/citations/18422345 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/18422345 |
| http://purl.uniprot.org/citations/18422345 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/18422345 |