6-phosphogluconate dehydrogenase

Details 6-phosphogluconate dehydrogenase 6-phosphogluconate dehydrogenase

2000-05-31

2001-10-30

Slobodyansky, Elizabeth (Department: 1652)

Chemistry: molecular biology and microbiology

Enzyme , proenzyme; compositions thereof; process for...

Oxidoreductase

C530S324000

Reexamination Certificate

active

06309866

ABSTRACT:

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, the invention relates to polynucleotides and polypeptides of the dehydrogenase family, as well as their variants, hereinafter referred to as “6-phosphogluconate dehydrogenase,” “6-phosphogluconate dehydrogenase polynucleotide(s),” and “6-phosphogluconate dehydrogenase polypeptide(s).”
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
Streptococcus 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 few decades. 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 phenomenon has created an unmet medical need and demand for new anti-microbial agents, vaccines, drug screening methods, and diagnostic tests for this organism.
Moreover, the drug discovery process is currently undergoing a fundamental revolution as it embraces “functional genomics,” that is, high throughput genome- or gene-based biology. This approach is rapidly superseding earlier approaches based on “positional cloning” and other methods. Functional genomics relies heavily on the various tools of bioinformatics to identify gene sequences of potential interest from the many molecular biology databases now available as well as from other sources. There is a continuing and significant need to identify and characterize further genes and other polynucleotides sequences and their related polypeptides, as targets for drug discovery.
Clearly, there exists a need for polynucleotides and polypeptides, such as the 6-phosphogluconate dehydrogenase embodiments of the invention, that have a present benefit of, among other things, being useful to screen compounds for antibiotic activity. Such factors are also useful 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 to find ways to prevent, ameliorate or correct such infection, dysfunction and disease.
Certain of the polypeptides of the invention possess significant amino acid sequence homology to a known Lactococcus lactis 6-phosphogluconate dehydrogenase U74322 protein. (Ohara H, et al. Biosci Biotechnol Biochem. 1996 60(4):692-6933; Gilmour MN, et al J. Bacteriol 1987 169(11):5247-5257)
SUMMARY OF THE INVENTION
The present invention relates to 6-phosphogluconate dehydrogenase, in particular 6-phosphogluconate dehydrogenase polypeptides and 6-phosphogluconate dehydrogenase polynucleotides, recombinant materials and methods for their production. In another aspect, the invention relates to methods for using such polypeptides and polynucleotides, including the treatment of microbial diseases, amongst others. In a further aspect, the invention: relates to methods for identifying agonists and antagonists using the materials provided by the invention, and for treating microbial infections and conditions associated with such infections with the identified compounds. In a still further aspect, the invention relates to diagnostic assays for detecting diseases associated with microbial infections and conditions associated with such infections, such as assays for detecting 6-phosphogluconate dehydrogenase expression or activity.
Various changes and modifications within the spirit and scope of the disclosed invention will become readily apparent to those skilled in the art from reading the following descriptions and from reading the other parts of the present disclosure.
DESCRIPTION OF THE INVENTION
The invention relates to 6-phosphogluconate dehydrogenase polypeptides and polynucleotides as described in greater detail below. In particular, the invention relates to polypeptides and polynucleotides of a 6-phosphogluconate dehydrogenase of
Streptococcus pneumoniae,
which is related by amino acid sequence homology to Lactococcus lactis 6-phosphogluconate dehydrogenase U74322 polypeptide. The invention relates especially to 6-phosphogluconate dehydrogenase having the nucleotide and amino acid sequences set out in Table 1 as SEQ ID NO: 1 and SEQ ID NO: 2 respectively.
TABLE 1
6-phosphogluconate dehydrogenase Polynucleotide
and Polypeptide Sequences
(A)
Streptococcus pneumoniae
6-phosphogluconate
dehydrogenase polynucleotide sequence [SEQ ID NO:1].
5′-ACCCGATCAAATGACAAAAGCTAACTTTGGTGTCGTAGGTATGGCCGTAA

TGGGTCGTAACCTTGCCCTTAATATTGAATCWCGTGGTTACACAGTTGCT

ATCTACAACCGTAGTAAAGAAAAAACGGAAGATGTGATTGCTTGCCATCC

TGAAAAGAACTTTGTACCAAGCTATGACGTTGAAAGTTTTGTAAACTCAA

TCGAAAAACCTCGTCGTATCATGCTGATGGTTCAAGCTGGACCTGGTACA

GATGCTACTATCCAAGCCCTTCTTCCACACCTTGACAAGGGTGATATCTT

GATTGACGGWGGAAATACTTTCTACAAAGATACCATCCGTCGTAATGAAG

AATTGGCAAACTCWGGTATCAACTTTATCGGTACTGGRGTTTCTGGTGGT

GAAAAAGGTGCCCTTGAAGGTCCTTCTATCATGCCTGGTGGACAAAAAGA

RGCCTACGAATTGGTTGCGGATGTTCTTGAAGAAATCTCAGCTAAAGCAC

CAGAAGATGGCAARCCATGTGTGACTTACATCGGTCCTGATGGAGCTGGT

CACTATGTGAAAATGGTTCACAATGGTATTGAGTACGGTGATATGCAATT

GATCGCAGAAAGCTATGACTTGATGCAACACTTGCTAGGCCTTTCTGCAG

AAGATATGGCTGAAATCTTTACTGAGTGGAACAAGGGTGAATTAGACAGC

TACTTGATTGAAATCACAGCTGATATCTTGAGCCGTAAAGACGATGAAGG

CCAAGATGGACCAATCGTAGACTACATCCTTGATGCTGCAGGTAACAAGG

GAACTGGTAAATGGACTAGCCAATCATCTCTTGACCTTGGTGTACCATTG

TCACTGATTACTGAGTCAGTGTTTGCACGCTACATTTCAACTTACAAAGA

AGAACGTGTACATGCTAGCAAGGTGCTTCCAAAACCAGCTGCCTTCAACT

TTGAAGGAGACAAGGCTGAATTGATTGAAAAGATCCGTCAAGCCCTTTAC

TTCTCAAAAATCATTTOATACGCACAAGGATTTGCTCAATTGCGTGTAGC

CTCTAAAGAAAACAACTGGAACTTGCCATTTGCAGATATCGCATCTATCT

GGCGTGATGGCTGTATCATCCGTTCTCGTTTCTTGCAAAAGATTACAGAT

GCTTACAACCGCGATGCAGATCTTGCCAACCTTCTTTTGGACGAGTACTT

CTTGGATGTTACTGCTAAGTACCAACAAGCAGTACGTGATATCGTAGCTC

TTGCGGTTCAAGCAGGTGTGCCAGTGCCAACTTTCTCAGCAGCTATTACT

TACTTTGATAGCTACCGTTCAGCTGACCTTCCAGCTAACTTGATCCAAGC

ACAACGTGACTACTTTGGTGCTCACACTTACCAACGTAAAGACAAAGAAG

GAACCTTCCACTACTCTTGGTATGACGAAAAATAAGTAGGTCAGCCATGG

GGAAACGGATTTTATTACTTGAGAAAGAACGAAATCTAGCTCATTTTTTA

AGTTTGGAACTCCAGAAAGAGCAGTATCGGGTTGATCTGGTAGAGGAGGG

GCAAAAAGCCCTCTCCATGGCTCTTCAGACAGACTATGATTTGATTTTAT

TGAACGTTAATCTGGGAGATATGATGGCTCAGGATTTTGCAGAAAAATTG

AGCCGAACTAAACCTGCCTCAGTCATCATGATTTTAGATCATTGGGAAGA

CTTGCAAGAAGAGCTGGAAGTTGTTCAGCGTTTTGCAGTTTCATACATCT

ATAAGCCAGTCCTTATCGAAAATCTGGTAGCGCGTATTTCGGCRATCTTC

CGAGGTCGGGACTTCATTGATCAACACTGCAGTCTGATGAAAGTTCCAAG

GACCTACCGCAATCTTAGGATAGATGTTGAACATCACACGGTTTATCGTG

GTGAAGAGATGATTGCTCTGACCCGCCGTGAGTATGACCTTTTGGCGACA

CTTATGGGAAGCAAGAAAGTATTGACTCGTGAGCAATTGTTGGAAAGTGT

TTGGAAGTATGAAAGTGCGACCGAGACAAATATCGTAGATGTCTATATCC

GCTATCTACGGAGCAAGCTTGATGTTAAAGGCCAAAA-3′

(B)
Streptococcus pneumoniae
6-phosphogluconate
dehydrogenase polypepfide sequence deduced from a
polynucleotide sequence in this table [SEQ ID NO:2].
NH
2
-MTKANFGVVGMAVMGRNLALNIESRGYTVAIYNRSKEKTEDVIACHPEKN

FVPSYDVESFVNSIEKFRRIMLMVQAGPGTDATIQALLPHLDKGDILIDG

GNTFYKDTIRRNEELANSGINFIGTGVSGGEKGALEGPSIMPGGQKEAYE

LVADVLEEISAKAPEDGKPCVTYIGPDGAGHYVKMVHNGIEYGDMQLIAE

Affiliated with

Also associated with

Rating

6-phosphogluconate dehydrogenase does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with 6-phosphogluconate dehydrogenase, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 6-phosphogluconate dehydrogenase will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2587543