title: Histidine modification and mutagenesis point to the involvement of a large conformational change in the mechanism of action of phage lambda lysozyme.
abstract: Phage lambda lysozyme (lambdaL) is structurally related to other known lysozymes but its mechanism of action is different from the classical lysozyme mechanism, acting as a transglycosidase rather than a hydrolase. As two conformations have been revealed by the crystal structure, we investigated the effect of mutating and modifying a histidine located near to or far from the active site in the respective closed and open conformations. Whereas its asparagine mutation has little or no effect on activity, its N-carbethoxylation inactivates the enzyme. This provide further evidence for the involvement of the closed conformation and for the need of conformational mobility in lambdaL function.
authors.affiliation: Université Catholique de Louvain, Laboratoire de Biochimie Physique et des Biopolymères, Place L. Pasteur 1-1B, B-1348, Louvain-la-Neuve, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Evrard
authors.forename: J
authors.initials: J
authors.lastname: Fastrez
authors.forename: P
authors.initials: P
authors.lastname: Soumillion
mesh_terms: D010582:Bacteriophage lambda / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D004047:Diethyl Pyrocarbonate / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D004795:Enzyme Stability / Q000187:drug effects / Q000235:genetics; D006639:Histidine / Q000235:genetics* / Q000378:metabolism*; D008958:Models, Molecular; D009113:Muramidase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed / Q000235:genetics*; D011487:Protein Conformation / Q000187:drug effects; D014764:Viral Proteins / Q000235:genetics
chemical_list: D014764:Viral Proteins; D006639:Histidine; D009113:Muramidase; D004047:Diethyl Pyrocarbonate