Abstract: The present invention is based on the discovery that a polypeptide containing the JAB subunit or the JAM domain has peptidase activity, e.g., isopeptidase activity. The present invention provides polypeptides and crystalline polypeptides containing the JAM domain and methods of using such polypeptides to screen for agents capable of affecting the peptidase activity of the polypeptides. The present invention also provides methods of using the JAM domain for rational drug design or identifying agents capable of affecting the peptidase activity of the JAM domain.

Abstract: Methods for identifying agents that can increase or decrease the isopeptidase activity of a COP9 signalsome (CSN) are provided, as are agent identified using such screening assays. In addition, methods of ameliorating a pathologic condition such as a cancer or an autoimmune disease in a subject by modulating the CSN isopeptidase activity are provided, as are medicaments useful for treating a subject having such a condition.

Abstract: Mutants of 2,5-diketo-D-gluconic acid reductase A, an enzyme used to produce 2-keto-L-gulonic acid, a precursor of ascorbic acid (vitamin C) are prepared by site-directed mutagenesis. These mutants have increased catalytic activity, increased expression levels, and/or enhanced temperature stability.

Abstract: The present invention provides an ?-keto acid reductase isolated from Leuconostoc mesenteroides subsp. dextranicum, and a DNA encoding the reductase. The enzyme and homologs thereof reduce ?-keto acids under the presence of NADH to produce optically active ?-hydroxy acids. The ?-hydroxy acids of the present invention include optically active mandelic acid derivatives of formula II.

Abstract: Disclosed is a water-soluble PQQGDH wherein two subunits are linked together via a disulfide bond. The water-soluble PQQGDH of the invention exhibits improved thermal stability.

Abstract: The invention is directed to polypeptides having P450 activity, polynucleotides encoding the polypeptides, antibodies that bind to these polypeptides, and methods for making and using these polynucleotides and polypeptides. The P450 enzymes can be used to catalyze the hydrolysis of epoxides and arene oxides to their corresponding diols.

Abstract: The present invention relates to canine COX-1 and COX-2 proteins; to canine COX-1 and COX-2 nucleic acid molecules, including those that encode such COX-1 and COX-2 proteins, respectively; to antibodies raised against such proteins; and to compounds that inhibit the activity of such proteins. The present invention also includes methods to obtain such proteins, nucleic acid molecules, antibodies, and inhibitory compounds. The present invention also includes therapeutic compositions comprising such inhibitory compounds, particularly those that specifically inhibit COX-2 activity, as well as the use of such therapeutic compositions to treat animals.

Abstract: Glucose oxidase enzymes are provided, including novel variants of galactose oxidase enzymes. The polynucleotides that encode these novel variants can be expressed in recombinant host cell expression systems. The novel variant oxidase enzymes are capable of oxidizing compounds towards which wild-type galactose oxidase (e.g. D-galactose: oxygen 6-oxidoreductase, GAO; EC 1.1.3.9) has little or no activity. Preferred galactose oxidase variants are those which that have improved capability to oxidize secondary alcohols and/or D-glucose relative to the wild-type enzyme.

Abstract: A process for oxidizing a substrate which is an acyclic or cyclic terpene, or a cycloalkene; or a substituted derivative thereof, which process comprises oxidizing said compound with a mutant haem-containing enzyme, the mutant comprising the substitution of an amino acid in the active site by an amino acid with a less polar side-chain. The enzyme is typically P450cam or P450BM-3. Cells and libraries of cells in which the process can be carried out or which can be used to select advantageous mutant enzymes are also provided.

Abstract: This invention provides (R)-2-octanol dehydrogenase that catalyzes oxidation-reduction reaction using NAD+ (NADH) as a coenzyme and the genes that encodes them. The enzymes of this invention can be obtained from microorganisms such as the genera Pichia, Candida, and Ogataea, and so on. It is possible to produce alcohols, in particular, alcohols such as (S)-4-halo-3-hydroxybutyric acid esters and (R)-propoxybenzene derivatives by reducing ketones with this (R)-2-octanol dehydrogenase. Moreover, the (R)-2-octanol dehydrogenase of this invention is excellent in activity and stereoselectivity.

Abstract: The present invention is directed to a nucleotide sequence encoding D-amino oxidase (D-AAO, EC 1.4.3.3) from Arthrobacter protophormiae. This may be inserted into an expression and used to transform a microbial host. The transformed microbial hosts ecomically produce D-AAO which may be used to oxidize D-amino acids.

Abstract: A fibrinolytically active metalloproteinase polypeptide (called “novel acting thrombolytic”) which is useful for blood clot lysis in vivo and methods and materials for its production by recombinant expression are described.

Abstract: The cDNA sequence of the human 9-cis-retinol dehydrogenase enzyme is disclosed.

Abstract: Protein complexes are provided comprising COX1 and one or more proteins selected from the group consisting of THR S14 and Opa1. The protein complexes are useful in screening assays for identifying compounds effective in modulating the protein complexes and in treating and/or preventing diseases and disorders associated with COX1 and its interacting partner proteins. In addition, methods of detecting the protein complexes and modulating the functions and activities of the protein complexes or interacting members thereof are also provided.

Abstract: This invention relates to the expression of improved polynucleotide and polypeptide sequences encoding for eukaryotic enzymes, particularly oxidase enzymes. The enzymes are advantageously produced in conventional or facile expression systems. Various methods for directed evolution of polynucleotide sequences can be used to obtain the improved sequences. The improved characteristics of the polypeptides or proteins generated in this manner include improved expression, enhanced activity toward one or more substrates, and increased thermal stability. In a particular embodiment, the invention relates to improved expression of the galactose oxidase gene and galactose oxidase enzymes. GAO mutants that are highly active and/or thermostable are disclosed.

Abstract: Novel genes have been isolated which encode cytochrome P450 and NADPH reductase enzymes of the ?-hydroxylase complex of C. tropicalis 20336. Vectors including these genes, transfected host cells and transformed host cells are provided. Methods of producing of cytochrome P450 and NADPH reductase enzymes are also provided which involve transforming a host cell with a gene encoding these enzymes and culturing the cells. Methods of increasing the production of a dicarboxylic acid and methods of increasing production of the aforementioned enzymes are also provided which involve increasing in the host cell the number of genes encoding these enzymes. A method for discriminating members of a gene family by quantifying the expression of genes is also provided.

Abstract: Genes have been isolated from a variety of bacteria encoding Baeyer-Villiger monooxygenase activity. The genes and their products are useful for the conversion of ketones to the corresponding esters. A series of motifs, common to all genes, has been identified as diagnostic for genes encoding proteins of this activity.

Abstract: This invention relates to the expression of improved polynucleotide and polypeptide sequences encoding for eukaryotic enzymes, particularly oxidase enzymes. The enzymes are advantagoeusly produced in conventional or facile expression systems. Various methods for directed evolution of polynucleotide sequences can be used to obtain the improved sequences. The improved characteristics of the polypeptides or proteins generated in this manner include improved expression, enhanced activity toward one or more substrates, and increased thermal stability. In a particular embodiment, the invention relates to improved expression of the galactose oxidase gene and galactose oxidase enzymes. GAO mutants that are highly active and/or thermostable are disclosed.

Abstract: The present invention provides soluble cytochrome p450 reductase (CPR) proteins from Candida sp. having an altered N-terminal region which results in reduced hydrophobicity of the N-terminal region. Also provided are host cells comprising the subject soluble CPR proteins. In addition, the present invention provides nucleotide and corresponding amino acid sequences for soluble CPR proteins and vectors comprising the nucleotide sequences. Methods for producing a soluble CPR, for increasing production of a dicarboxylic acid, and for detecting a cytochrome P450 are also provided.

Abstract: The present invention relates to a newly identified human PGP synthase. The invention also relates to polynucleotides encoding the PGP synthase. The invention further relates to methods using the PGP synthase polypeptides and polynucleotides as a target for diagnosis and treatment in PGP synthase-mediated or -related disorders. The invention further relates to drug-screening methods using the PGP synthase polypeptides and polynucleotides to identify agonists and antagonists for diagnosis and treatment. The invention further encompasses agonists and antagonists based on the PGP synthase polypeptides and polynucleotides. The invention further relates to procedures for producing the PGP synthase polypeptides and polynucleotides.