Novel purified polypeptides from streptococcus pneumoniae
AssigneeAffinium Pharmaceuticals, Inc.
InventorsAled Edwards, Akil Dharamsi, Masoud Vedadi, Matthew Kimber
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Abstract
The present invention relates to novel drug targets for pathogenic bacteria. Accordingly, the invention provides purified protein comprising the amino acid sequence set forth in SEQ ID NO: 4. The invention also provides biochemical and biophysical characteristics of the polypeptides of the invention.
Claims20
A composition comprising an isolated, recombinant polypeptide, wherein the polypeptide comprises:
- (a) an amino acid sequence set forth in SEQ ID NO:
- 2 or SEQ ID NO:
- 4;
- (b) an amino acid sequence having at least about 95% identity with the amino acid sequence set forth in SEQ ID NO:
- 2 or SEQ ID NO:
- 4;
- or (c) an amino acid sequence encoded by a polynucleotide that hybridizes under stringent conditions to the complementary strand of a polynucleotide having SEQ ID NO:
- 1 or SEQ ID NO:
- 3 and has at least one biological activity of UDP-N-acetylglucosamine 1-carboxyvinyltransferase from S. pneumoniae;
- and wherein the polypeptide of (a), (b) or (c) is at least about 90% pure in a sample of the composition.
The composition of claim 1, wherein the polypeptide is at least about 95% pure as determined by gel electrophoresis.
The crystallized composition of claim 5, further comprising a co-factor.
The method of claim 10, wherein the crystallized composition further comprises a small organic molecule.
A method for identifying a modulator of a polypeptide, the method comprising:
- (a) providing the three-dimensional coordinates for a plurality of the amino acids of a polypeptide comprising (1) an amino acid sequence set forth in SEQ ID NO:
- 2 or SEQ ID NO:
- 4;
- (2) an amino acid sequence having at least about 95% identity with the amino acid sequence set forth in SEQ ID NO:
- 2 or SEQ ID NO:
- 4;
- or (3) an amino acid sequence encoded by a polynucleotide that hybridizes under stringent conditions to the complementary strand of a polynucleotide having SEQ ID NO:
- 1 or SEQ ID NO:
- 3 and has at least one biological activity of UDP-N-acetylglucosamine 1-carboxyvinyltransferase from S. pneumoniae;
- (b) identifying a druggable region of the polypeptide;
- and
- (c) selecting at least one potential modulator by using the three dimensional coordinates to determine if a chemical entity may bind to or interfere with the druggable region.
The method of claim 13, wherein the chemical entity is a small molecule.
A method for designing a modulator for the prevention or treatment of a S. pneumoniae related disease or disorder, comprising:
- (a) providing the three-dimensional coordinates for a plurality of the amino acids of a polypeptide comprising (1) an amino acid sequence set forth in SEQ ID NO:
- 2 or SEQ ID NO:
- 4;
- (2) an amino acid sequence having at least about 95% identity with the amino acid sequence set forth in SEQ ID NO:
- 2 or SEQ ID NO:
- 4;
- or (3) an amino acid sequence encoded by a polynucleotide that hybridizes under stringent conditions to the complementary strand of a polynucleotide having SEQ ID NO:
- 1 or SEQ ID NO:
- 3 and has at least one biological activity of UDP-N-acetylglucosamine 1-carboxyvinyltransferase from S. pneunmoniae;
- and
- (b) designing a potential modulator for the prevention or treatment of a S. pneumoniae related disease or disorder by employing the three-dimensional structure in a rational drug design method.
The method of claim 17, further comprising
- (a) contacting S. pneumoniae or a polypeptide comprising (1) an amino acid sequence set forth in SEQ ID NO:
- 2 or SEQ ID NO:
- 4;
- (2) an amino acid sequence having at least about 95% identity with the amino acid sequence set forth in SEQ ID NO:
- 2 or SEQ ID NO:
- 4;
- or (3) an amino acid sequence encoded by a polynucleotide that hybridizes under stringent conditions to the complementary strand of a polynucleotide having SEQ ID NO:
- 1 or SEQ ID NO:
- 3 and has at least one biological activity of UDP-N-acetylglucosamine 1-carboxyvinyltransferase from S. pneumoniae with the potential modulator;
- and
- (b) assaying the activity of the polypeptide or determining the viability of S. pneumoinae after contact with the modulator, wherein a change in the activity of the polypeptide or the viability of S. pneumoniae indicates that the modulator may be useful for prevention or treatment of a S. pneumoniae related disease or disorder.
Dependencies are inferred from the claim text.