Abstract: Provided are methods and compositions useful in detecting protease activity in a sample, as well as methods of identifying agents that modulate protease activity. The methods and compositions provide a modified luciferase polynucleotide sequence and a luciferase polypeptide containing protease recognition sequences, wherein cleavage of the recognition sequence by a protease inhibits luciferase activity. Further provided are methods and compositions for detecting and modulating caspase activity and apoptosis.

Abstract: The invention relates to methods and materials for use in the typing, diagnosis, prevention and/or treatment of prion disease.

Abstract: The present invention relates to the identification of novel serine proteases in Gram-positive microorganisms. The present invention provides the nucleic acid and amino acid sequences for the Bacillus subtilis serine proteases SP1, SP2, SP3, SP4 and SP5. The present invention also provides host cells having a mutation or deletion of part or all of the gene encoding SP1, SP2, SP3, SP4 and SP5. The present invention also provides host cells further comprising nucleic acid encoding desired heterologous proteins such as enzymes. The present invention also provides a cleaning composition comprising a serine protease of the present invention.

Abstract: Novel human polynucleotide and polypeptide sequences are disclosed that can be used in therapeutic, diagnostic, and pharmacogenomic applications.

Abstract: Disclosed is a pO157 plasmid-specified polypeptide found in E. coli EDL933and other enterohemorrhagic E. coli that binds to and cleaves C1-esterase inhibitor. Also disclosed are methods employing the polypeptide for diagnosing and treating colitis or hemolytic uremic syndrome, and methods of detecting potential therapeutics.

Abstract: The cDNA which codes for factor XIIIa has been isolated using a cDNA bank from human placenta and probes constructed on the basis of the amino acid sequence of factor XIIIa peptide fragments. It is possible with this cDNA not only to obtain factor XIIIa by gene manipulation in high purity but also to prepare diagnostic aids which permit the analysis of genetic factor XIIIa defects. Furthermore, it is possible on the basis of the amino acid sequence to prepare antibodies which are suitable for diagnostic aids and antibody columns.

Abstract: The present invention provides isolated polypeptides, dipeptidylpeptidases, active analogs, active fragments, or active modifications thereof, having amidolytic activity for cleavage of a peptide bond between the second and third amino acids from the N-terminal end of a target polypeptide, wherein the target polypeptide has an aliphatic or an aromatic residue as a substituent on the ?-carbon atom of the second amino acid from the N-terminal end of the peptide. Isolated nucleic acids encoding dipeptidylpeptidases are also provided, as are methods of reducing growth of a bacterium by inhibiting a dipeptidylpeptidase.

Abstract: The present invention relates to the identification of novel serine proteases in Gram-positive microorganisms. The present invention provides the nucleic acid and amino acid sequences for the Bacillus subtilis serine proteases SP1, SP2, SP3, SP4 and SP5. The present invention also provides host cells having a mutation or deletion of part or all of the gene encoding SP1, SP2, SP3, SP4 and SP5. The present invention also provides host cells further comprising nucleic acid encoding desired heterologous proteins such as enzymes. The present invention also provides a cleaning composition comprising a serine protease of the present invention.

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: The present invention provides a process for economically producing N-acetylneuraminic acid without using expensive materials such as pyruvic acid and phosphoenolpyruvic acid. The process comprises: allowing (i) a culture of a microorganism having N-acetylneuraminic acid aldolase activity or N-acetylneuraminic acid synthetase activity, or a treated matter of the culture, (ii) a culture of a microorganism capable of producing pyruvic acid or a treated matter of the culture, or a culture of a microorganism capable of producing phosphoenolpyruvic acid or a treated matter of the culture, (iii) N-acetylmannosamine, and (iv) an energy source which is necessary for the formation of pyruvic acid or phosphoenolpyruvic acid to be present in an aqueous medium to form and accumulate N-acetylneuraminic acid in the aqueous medium; and recovering N-acetylneuraminic acid from the aqueous medium.

Abstract: Novel human polynucleotide and polypeptide sequences are disclosed that can be used in therapeutic, diagnostic, and pharmacogenomic applications.

Abstract: The present invention provides novel human caspase-12 polynucleotides and polypeptides; constructs and recombinant host cells incorporating the polynucleotides; the human caspase-12 polypeptides encoded by the polynucleotides; antibodies to the polypeptides; and methods of making and using all of the foregoing.

Abstract: The present invention relates to the identification of novel serine proteases in Gram-positive microorganisms. The present invention provides the nucleic acid and amino acid sequences for the Bacillus subtilis serine proteases SP1, SP2, SP3, SP4 and SP5. The present invention also provides host cells having a mutation or deletion of part or all of the gene encoding SP1, SP2, SP3, SP4 and SP5. The present invention also provides host cells further comprising nucleic acid encoding desired heterologous proteins such as enzymes. The present invention also provides a cleaning composition comprising a serine protease of the present invention.

Abstract: The invention provides molecules that encode sphingosine kinase, the enzyme that catalyzes the phosphorylation of sphingosine to form sphingosine-1-phosphate (SPP). Vectors and host cells which express sphingosine kinase are also provided, as are methods for evaluating the stimulatory or inhibitory effects of agents on sphingosine kinase production and activity.

Abstract: The present invention provides the enzyme and enzymatic procedures for cleaving the &bgr; secretase cleavage site of the APP protein and associated nucleic acids, peptides, vectors, cells and cell isolates and assays. The invention further provides a modified APP protein and associated nucleic acids, peptides, vectors, cells, and cell isolates, and assays that are particularly useful for identifying candidate therapeutics for treatment or prevention of Alzheimer's disease.

Abstract: The present invention provides a cyclic lipopeptide acylase which may effectively deacylate the acyl side chain of a cyclic lipopeptide compound, specifically FR901379 Substance or its analog thereof shown by the following general formula [I], and a process for production of a cyclic peptide compound which comprises the use of said acylase.

Abstract: The present invention provides compounds useful for the detection of the enzyme tripeptidyl protease I (TPP-1). The invention also provides methods of making such compounds, methods of using such compounds, and kits and compositions containing such compounds. In one embodiment, Gly-L-Pro-L-Ser-1-anthraquinonylhydrazide, in combination with p-anisaldehyde, is used to detect TPP-1.

Abstract: The present invention provides amino acid sequences of peptides that are encoded by genes within the human genome, the protease peptides of the present invention. The present invention specifically provides isolated peptide and nucleic acid molecules, methods of identifying orthologs and paralogs of the protease peptides, and methods of identifying modulators of the protease peptides.

Abstract: Methods and compositions that can reduce the symptoms of autism in a human patient comprising administering a physiologically effective amount of one or both of a purified casomorphin inhibitor selected from the group consisting of a casomorphinase and a casomorphin ligand, and a physiologically effective amount of a purified gluteomorphin inhibitor selected from the group consisting of a gluteomorphinase and a gluteomorphin ligand, to a human patient in sufficient quantities to reduce the effects of the autism. In some embodiments, the compositions and methods further comprise a physiologically effective amount of an enkephalin inhibitor, preferably an enkephalinase, and a physiologically effective amount of an endorphin inhibitor, preferably an endorphinase.

Abstract: The present invention provides a method for producing desired proteins or chemicals in fungal host cells, which comprise modulating the nucleic acid encoding proteins associated with hyphal growth. The amino acid and nucleic acid sequences of hbrA and hbrB are provided.

Abstract: The object of the present invention is to provide Koji mold aminopeptidases capable of efficiently hydrolyzing persistent peptides and also genes encoding the aminopeptidases. The present invention provides Aspergillus nidulans aminopeptidase and nucleic acid molecules encoding it. In particular, the present invention provides a protein having an amino acid sequence represented by amino acid Nos. 1 to 519 in SEQ ID NO: 2, or a protein containing the substitution, deletion, insertion, addition or inversion of one or more amino acids in said sequence, and which protein has an activity of catalyzing the reaction for releasing an amino acid at an N-terminal of a peptide, and nucleic acid molecules encoding them.

Abstract: Methods and compositions that can reduce the symptoms of autism in a human patient comprising administering a physiologically effective amount of one or both of a purified casomorphin inhibitor selected from the group consisting of a casomorphinase and a casomorphin ligand, and a physiologically effective amount of a purified gluteomorphin inhibitor selected from the group consisting of a gluteomorphinase and a gluteomorphin ligand, to a human patient in sufficient quantities to reduce the effects of the autism. In some embodiments, the compositions and methods further comprise a physiologically effective amount of an enkephalin inhibitor, preferably an enkephalinase, and a physiologically effective amount of an endorphin inhibitor, preferably an endorphinase.

Abstract: The invention relates to polynucleotides corresponding to the ccpA2 gene and which encode a CcpA2 catabolite control protein, methods of producing L-amino acids, and methods of screening for polynucleotides which encode proteins having CcpA2 catabolite control activity.

Abstract: DNA and recombinant DNA that encode a peptide-forming enzyme, a method for producing a peptide-forming enzyme, and a method for producing a dipeptide are disclosed. A method for producing a dipeptide includes producing a dipeptide from a carboxy component and an amine component by using a culture of a microbe belonging to the genus Sphingobacterium and having the ability to form the dipeptide from the carboxy component and the amine component, a microbial cell separated from the culture, treated microbial cell product of the microbe or a peptide-forming enzyme derived from the microbe.

Abstract: The present invention relates to an isolated and purified DNA comprising a nucleotide sequence that encodes a polypeptide functionally involved in the DNA mismatch repair system of a plant.

Abstract: The present invention relates to alkaline proteases having high specific activity and strong oxidant resistance. The present invention also relates to alkaline proteases having excellent detergency that is to be added to a detergent.

Abstract: This invention provides tandem fluorescent protein construct including a donor fluorescent protein moiety, an acceptor fluorescent protein moiety and a linker moiety that couples the donor and acceptor moieties. The donor and acceptor moieties exhibit fluorescence resonance energy transfer which is eliminated upon cleavage. The constructs are useful in enzymatic assays.

Abstract: Novel proteins which belong to the papain family and are cysteine proteinase enzymes (the cysteine proteinase enzymes are expected to be involved in the turnover of intracellular proteins, antigen presentation, prohormone activation, bone remodeling, etc. and to play important roles in a variety of pathological conditions such as Alzheimer's disease, pulmonary emphysema, rheumatoid arthritis, muscular dystrophy, osteoporosis, neurodegenerative disease, and cancer invasion and metastasis), together with genes encoding the proteins and antibodies against the proteins, can be conveniently used in elucidating the function of a cysteine proteinase involved in various diseases and disorders, especially cancers, thereby not only disclosing critical mechanism leading to such diseases and disorders but also researching and developing therapy and therapeutic drugs thereagainst.

Abstract: The present invention relates to a novel enzyme (&agr;-GARE) which releases an amino acid residue having a glycated &agr;-amino group (&agr;-GA) from a glycated protein etc. and to bacterial strains producing the same. Examples of the bacterial strains include Corynebacterium ureolyticum KDK1002 (FERM P-17135) and Pseudomonas alcaligenes KDK1001 (FERM P-17133). The &agr;-GARE is contained in the culture supernatant of these strains and &agr;-GA can be released from a glycated peptide by using the same, as shown in FIG. 1.

Abstract: This invention describes a method of removing N-terminal alanine residues from polypeptides, preferably recombinant proteins, using an aminopeptidase derived from the marine bacterium Aeromonas proteolytica. Accordingly, Aeromonas aminopeptidase (AAP; E.C. 3.4.11.10) can be used to remove N-terminal alanyl residues from derivatives of human somatotropin (hST, human growth hormone, or hGH), porcine somatotropin (pST), and bovine somatotropin (bST), for example, to yield proteins having their native amino acid sequences. The enzyme reactions can be carried out in free solution, or the AAP can be immobilized on a solid support, for reactions carried out in vitro. An efficient method for converting Ala-hGH to hGH, for example, comprises expression of Ala-hGH in E. coli, recovery of inclusion bodies, solubilization and refolding in detergent, detergent removal by ultrafiltration, selective precipitation, enzyme cleavage, followed by two column chromatography steps.

Abstract: This invention relates to a soluble form of PHEX, PHEX being a type II integral membrane glycoprotein. This enzyme is the gene product of a phosphate-regulating gene with homologies to endopeptidases on the X chromosome. To produce a soluble form of PHEX, the transmembrane anchor domain has been modified to encode a signal peptidase coding sequence. The soluble PHEX therefore comprises the active ectodomain. An inactive mutant of PHEX is also an object of this invention. Both soluble and inactive mutant forms of PHEX can be used to screen ligands to PHEX. These ligands can also be used as substrates or inhibitors of PHEX. PHEX being phosphaturic, an inhibitor thereof will be used to treat phosphaturia and/or hypophosphatemia. On the opposite, a substrate for PHEX or PHEX itself can be used to treat hyperphosphatemia.

Abstract: A hyperthermostable protease having the amino acid sequence represented by the SEQ ID NO:1 of the Sequence Listing or a sequence derived therefrom by deletion, substitution, insertion or addition of one to several amino acid residues, a gene encoding the hyperthermostable protease, and a process for preparing the protease, aiming at providing by genetic engineering techniques a hyperthermophile protease which is advantageous for industrial use.

Abstract: The present invention provides novel nucleic acids, novel polypeptide sequences encoded by these nucleic acids and uses thereof.

Abstract: Hydrolyzed collagen type II powder compositions for inducing cartilage formation in an individual, method of preparing the compositions and use of the compositions in treating connective tissue disorder, replenishing skin viscoelasticity. The compositions are administered through an orally ingestible delivery medium for absorption into the gastrointestinal tract. The compositions are administered through a topical delivery medium for absorption into a dermis of the individual.

Abstract: The present invention is relates to a &ggr;-carboxylase from Conus snails, a nucleic acid sequence encoding the Conus &ggr;-carboxylase and to a method for using the nucleic acid or protein sequences for preparing &ggr;-carboxylated proteins.

Abstract: Novel human polynucleotide and polypeptide sequences are disclosed that can be used in therapeutic, diagnostic, and pharmacogenomic applications.

Abstract: The present invention is a substantially purified sortase-transamidase enzyme from Gram-positive bacteria, such as Staphylococcus aureus.

Abstract: The present invention provides a method of treatment of viral hemorrhagic fever with protein C. The claimed invention provides a needed therapy for a serious and debilitating disorder while avoiding complications such as bleeding tendency, toxicity and general side effects of currently available anti-coagulant agents.

Abstract: An enzyme solution obtained by cultivating Bacillus subtilis M2-4 strain highly heat-resistant peptidase activity such that the residual activity thereof after 1-hr heat treatment at 60 to 65° C. at pH 7 is substantially 100%. An enzyme preparation can be obtained by separating the enzyme protein from the enzyme solution. Using such enzyme solution or enzyme preparation as an active component, a proteolytic enzyme preparation can be prepared. The enzyme solution, the enzyme preparation and the proteolytic enzyme preparation have both high heat-resistance and great potency of hydrolyzing proteins into low molecules.

Abstract: The invention relates to a method for purifying at least one enzyme obtained in an excess fermentation of Clostridium histolyticum.

Abstract: The invention provides vitamin k-dependent polypeptides with enhanced membrane binding affinity. These polypeptides can be used to modulate clot formation in mammals. Methods of modulating clot formation in mammals are also described.

Abstract: Provided are isolated nucleic acids encoding a novel membrane derived caspase-3 and polypeptides expressed therefrom. In one embodiment, the nucleic acid expression vectors that produce membrane derived caspase-3 polypeptide may be introduced into host cells as a gene delivery vehicle. In other embodiments, methods are provided for treating pathological disorders caused by altered apoptosis, such as autoimmune disease, cancer, viral infections, and bacterial infections. Another aspect of the invention is the use of the isolated nucleic acid encoding membrane derived caspase-3 and polypeptides expressed therefrom as a means for promoting or inhibiting programmed cell death.

Abstract: The present invention relates to polynucleotide and polypeptide molecules, and variants thereof, for MAPP, a novel member of the Disintegrin Proteases. The polypeptides, and polynucleotides encoding them, are cell-cell interaction modulating and may be used for delivery and therapeutics. The present invention also includes antibodies to the MAPP polypeptides.

Abstract: An alkaline protease having the following properties; a gene encoding the same; a microorganism producing the same; and washing compositions containing the same; (i) acting over a broad pH value range of 4 to 13 and achieving, at pH 6 to 12, 80% or more the activity at the optimum pH value; (ii) when treated at 40° C. for 30 minutes, being stable over a pH value range of 6 to 11; (iii) having an isoelectric point of about 8.9 to 9.1; and (iv) having casein digesting activity that is not inhibited by oleic acid. The alkaline protease of the present invention is highly stable to various surface active agents and fatty acids, and exhibits high stability to oxidizing agents, and is therefore useful as an enzyme to be used in detergents for automatic dishwashers and laundry detergents, both containing bleaching components.

Abstract: Caspases are cysteinyl aspartate-specific proteinases, many of which play a central role in apoptosis. This invention relates to the identification of a new murine caspase and its human homologue. The new molecules are most related to human/murine caspase-2 and human caspase-9 and possesses all the typical amino acid residues of the caspases involved in catalysis, including the QACRG box, and contains no or only a very short prodomain. Northern blot analysis revealed that mRNA expression of the new caspase is predominant in skin.

Abstract: The invention is directed to the family of aggrecan degrading metallo proteases (ADMPs) that exhibit the ability to cleave the aggrecan core protein between amino acid residues Glu373-Ala374. The invention encompasses the nucleic acids encoding such enzymes, processes for production of recombinant ADMPs, compositions containing such enzymes, and the use of these enzymes in various assays and for the development of novel inhibitors for use as therapies for diseases involving aggrecanase-mediated degradation of cartilage or other aggrecanase-associated diseases.

Abstract: This invention relates to the discovery that toxicity to mustard may be evaluated by diagnostic test means disclosed herein. Upon electrophoretic separation (sodium dodocyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)) of buffered extract of human skin cells (normal human epidermal keratinocytes (NHEK)) which had been exposed to mustard-type chemical compounds a band at approximately 50,000 to 80,000 daltons molecular weight was found. The protein band constitutes a biomarker.

Abstract: The present invention provides the enzyme and enzymatic procedures for cleaving the &bgr; secretase cleavage site of the APP protein and associated nucleic acids, peptides, vectors, cells and cell isolates and assays. The invention further provides a modified APP protein and associated nucleic acids, peptides, vectors, cells, and cell isolates, and assays that are particularly useful for identifying candidate therapeutics for treatment or prevention of Alzheimer's disease.

Abstract: The present invention relates to a histaminase of vegetable origin to be used in the treatment of allergic and septic shock and inallergic asthma. The invention also regards the preparation of the histaminase for pharmaceutical use and the corresponding pharmaceutical compositions.

Abstract: The invention provides vitamin K-dependent polypeptides with enhanced membrane binding affinity. These polypeptides can be used to modulate clot formation in mammals. Methods of modulating clot formation in mammals are also described.