Amidotransferase, ratB, of streptococcus pneumoniae

Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...

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4353201, 4352523, 43525411, 435325, 435455, 435471, 536 231, 536 232, 536 234, 536 237, C12N 1510, C12N 1531, C12N 1552, C12N 1562, C12N 1563

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active

061365602

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 rat family, hereinafter referred to as "ratB".


BACKGROUND OF THE INVENTION

The Streptococci make up a medically important genera of microbes known to cause several types of disease in humans, including, for example, otitis media, conjunctivitis, pneumonia, bacteremia, meningitis, sinusitis, pleural empyema and endocarditis, and most particularly meningitis, such as for example infection of cerebrospinal fluid. Since its isolation more than 100 years ago, Streptococcus pneumoniae has been one of the more intensively studied microbes. For example, much of our early understanding that DNA is, in fact, the genetic material was predicated on the work of Griffith and of Avery, Macleod and McCarty using this microbe. Despite the vast amount of research with S. pneumoniae, many questions concerning the virulence of this microbe remain. It is particularly preferred to employ Streptococcal genes and gene products as targets for the development of antibiotics.
The frequency of Streptococcus pneumoniae infections has risen dramatically in the past 20 years. This has been attributed to the emergence of multiply antibiotic resistant strains and an increasing population of people with weakened immune systems. It is no longer uncommon to isolate Streptococcus pneumoniae strains which are resistant to some or all of the standard antibiotics. This has created a demand for both new anti-microbial agents and diagnostic tests for this organism.
The translation product of the ratb gene is one of at least two polypeptides that constitute an amidotransferase which catalyses the transfer of an amino group from a donor to Glu-tRNA(Gln) in order to form Gln-tRNA(Gln). The reaction is essential to bacteria that lack a glutaminyl-tRNA synthetase activity.
Clearly, there is a need for factors, such as the novel compounds of the invention, having a present benfit of being useful to screen compounds for antibiotic activity. Such factors may also be used to determine their role 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 Bacilus subtilis PET112-like protein.
Each patent application to which this invention claims priority is hereby incorporated by reference in its entirety.


SUMMARY OF THE INVENTION

It is an object of the invention to provide polypeptides that have been identified as novel ratb polypeptides by homology between the amino acid sequence set out in FIGS. 2 or 4 [SEQ ID NOS: 2 or 4] and a known amino acid sequence or sequences of other proteins such as Bacilus subtilis PET112-like protein.
It is a further object of the invention to provide polynucleotides that encode ratb polypeptides, particularly polynucleotides that encode the polypeptide herein designated ratb.
In a particularly preferred embodiment of the invention the polynucleotide comprises a region encoding ratb polypeptides comprising the sequence set out in FIGS. 1 or 3 [SEQ ID NOS: 1 or 3], or a variant thereof.
In another particularly preferred embodiment of the invention there is a novel ratb protein from Streptococcus pneumoniae comprising the amino acid sequence of FIGS. 2 or 4 [SEQ ID NOS:2 or 4], or a variant thereof.
In accordance with another aspect of the invention there is provided an isolated nucleic acid molecule encoding a mature polypeptide expressible by the Streptococcus pneumoniae 0100993 strain contained in NCIMB Deposit No. 40794.
A further aspect of the invention there are provided isolated nucleic acid molecules encoding ratb, par

REFERENCES:
Genbank Accession No. Z99107 AL009126, Kunst et al., U.S. National Library of Medicine, accessed by PTO on Apr. 6, 2000, Nov. 1997.

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