Mutations, site specific active sites

We have used a series of biocatalysts produced by site-directed mutations at the active site of L-phenylalanine dehydrogenase (PheDH) of Bacillus sphaericus, which expand the substrate specificity range beyond that of the wild-type enzyme, to catalyse oxidoreduc-tions involving various non-natural L-amino acids. These may be produced by enantiose-lective enzyme-catalysed reductive amination of the corresponding 2-oxoacid. Since the reaction is reversible, these biocatalysts may also be used to effect a kinetic resolution of a D,L racemic mixture. ... 

S. Oue, A. Okamoto, T. Yano, and H. Kaga-miyama, Redesigning the substrate specificity of an enzyme by cumulative effects of the mutations of non-active site residues,/. Biol. Chem. 1999, 274, 2344-2349. 

Subtilisin, 170 active site of, 171,173 autocorrelation function of, 216, 216 potential surfaces for, 218 site-specific mutations, 184, 185, 187-188 Sugars, see Oligosaccharides Surface-constrained solvent model, 125... 

Viruses that contain amino acid substitutions in the sialidase that impart resistance to the developed inhibitors have been isolated from serial passage of virus in the presence of drug in cell culture and from the clinical setting (reviewed in McKimm-Breschkin 2000 Zambon and Hayden 2001 Cinatl et al. 2007a Reece 2007). In addition, influenza B virus variants with reduced drug sensitivity have been isolated from previously untreated patients (Hurt et al. 2006 Hatakeyama et al. 2007). The types of mutations that are observed are sub-type specific. The mutations present in variants isolated from clinical samples are shown in Table 1, and their locations within the sialidase active site are shown diagrammatically in Fig. 9. 

Mutations in bacteria and mammalian cells (including some that result in human disease) have supported these conclusions. Facilitated diffusion and active transport resemble a substrate-enzyme reaction except that no covalent interaction occurs. These points of resemblance are as follows (1) There is a specific binding site for the solute. (2) The carrier is saturable, so it has a maximum rate of transport (V Figure 41-11). (3) There is a binding constant (Al) ) for the solute, and... 

Induced mutagenesis in Escherichia coli is an active process involving proteins with DNA replication, repair, and recombination functions. The available evidence suggests that mutations are generated at sites where DNA has been damaged and that they arise via an error-prone repair activity. In an attempt to understand what specific contributions to mutagenesis are made by DNA lesions, we have studied the mutational specificity of some carcinogens, such as benzo[a]pyrene and aflatoxin, whose chemical reactions with DNA are... 

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