Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing
Patent
1997-09-16
2000-06-27
Riley, Jezia
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
435 6, 435183, 4352523, 435 691, 4353201, 514 44, 530300, 530350, 5303881, 536 232, A01N 6100, C12N 900, A61K 3800, C07H 2102
Patent
active
060807172
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention relates to newly identified polynucleotides and polypeptides, and their production and uses, as well as their variants, agonists and antagonists, and their uses. In particular, in these and in other regards, the invention relates to novel polynucleotides and polypeptides of the tRNA synthetase family, hereinafter referred to as "tRNA synthetase".
BACKGROUND OF THE INVENTION
It is particularly preferred to employ Staphylococcal genes and gene products as targets for the development of antibiotics. The Staphylococci make up a medically important genera of microbes. They are known to produce two types of disease, invasive and toxigenic. Invasive infections are characterized generally by abscess formation effecting both skin surfaces and deep tissues. S. aureus is the second leading cause of bacteremia in cancer patients. Osteomyelitis, septic arthritis, septic thrombophlebitis and acute bacterial endocarditis are also relatively common. There are at least three clinical conditions resulting from the toxigenic properties of Staphylococci. The manifestation of these diseases result from the actions of exotoxins as opposed to tissue invasion and bacteremia. These conditions include: Staphylococcal food poisoning, scalded skin syndrome and toxic shock syndrome. The tRNA synthetases have a primary role in protein synthesis according to the following scheme:
Inhibition of this process leads to a reduction in the levels of charged tRNA and this triggers a cascade of responses known as the stringent response, the result of which is the induction of a state of dormancy in the organism. As such selective inhibitors of bacterial tRNA synthetase have potential as antibacterial agents. One example of such is mupirocin which is a selective inhibitor of isoleucyl tRNA synthetase. Isolation of tRNA synthetase allows for the identification and analysis of potential antibacterial targets to facilitate screening for antibacterial compounds
Isoleucyl tRNA synthetase, isolated from Staphylococcus aureus, has already been described (Chalker, A., F., Ward, J., M.,Fosberry, A., P. and Hodgson, J., E. 1994 Gene 141:103-108).
Clearly, there is a need for factors that may be used to screen compounds for antibiotic activity and which factors may also be used to determine their roles in pathogenesis of infection, dysfunction and disease. There is also a need for identification and characterization of such factors and their antagonists and agonists which can play a role in preventing, ameliorating or correcting infections, dysfunctions or diseases.
The polypeptides of the invention have amino acid sequence homology to a known Bacillus subtilis cysteinyl tRNA synthetase protein.
SUMMARY OF THE INVENTION
It is an object of the invention to provide polypeptides that have been identified as novel tRNA synthetase polypeptides by homology between the amino acid sequence set out in FIG. 2 and a known amino acid sequence or sequences of other proteins such as Bacillus subtilis cysteinyl tRNA synthetase protein.
It is a further object of the invention to provide polynucleotides that encode tRNA synthetase polypeptides, particularly polynucleotides that encode the polypeptide herein designated tRNA synthetase.
In a particularly preferred embodiment of this aspect of the invention the polynucleotide comprises a region encoding cysteinyl tRNA synthetase polypeptides comprising the sequence set out in FIG. 1 [SEQ ID NO:1], or a variant thereof.
In another particularly preferred embodiment of the invention there is a novel cysteinyl tRNA synthetase protein from Staphylococcus aureus comprising the amino acid sequence of FIG. 2 [SEQ ID NO:2], or a variant thereof.
In accordance with this aspect of the invention there is provided an isolated nucleic acid molecule encoding a mature polypeptide expressible by the Staphylococcus aureus WCUH 29 strain contained in NCIMB Deposit No. 40771.
In accordance with this aspect of the invention there are provided isolated nucleic acid molecules encoding tRNA synthetase, pa
REFERENCES:
patent: 5358862 (1994-10-01), Hardesty et al.
patent: 5798240 (1998-08-01), Martinis et al.
Kron, et al., "An immunodominant antigen of Brugia malayi is an asparaginyl-tRNA synthetase", FEBS Letters, 374 pp. 122-124 (1995).
Chalker, et al., "Analysis and toxic overexpression in Escherichia coli is a staphylococcal gene encoding isoleucyl-tRNA synthetase", Gene, 141, pp. 103-108 (1994).
Nilsen, et al., "Cloning and characterization of a potentially protective antigen in lymphatic filariasis", Proc. Natl. Acad. Sci. USA, 85, pp. 3604-3607 (1988).
Fleischmann, et al., "Whole-Genome Sequencing and Assembly of Haemophilus Influenzae Rd", Science, 269, pp. 496-512 (1995).
Seror, et al., "A mutant cysteinyl-tRNA synthetase affecting timing of chromosomal replication initiation in B. subtilis and conferring resistance to a protein kinase C inhibitor", The EMBO Journal, 13, No. 10 pp. 2472-2480 (1994).
Lake et al. "Investigations on the antiproliferative effects of amino acid antagonists targeting for aminoacyl-tRNA synthetases" Arch. Pharm. 322, pp. 847-852, 1989.
Hodgson John Edward
Lawlor Elizabeth Jane
Deibert Thomas S.
Gimmi Edward R.
King William T.
Riley Jezia
SmithKline Beecham p.l.c.
LandOfFree
Cysteinyl-tRNA synthetase from Staphylococcus aureus does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Cysteinyl-tRNA synthetase from Staphylococcus aureus, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Cysteinyl-tRNA synthetase from Staphylococcus aureus will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1784812