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Bioinformatics and structural characterization of a hypothetical protein from Streptococcus mutans: implication of antibiotic resistance.

Nan J, Brostromer E, Liu XY, Kristensen O, Su XD - PLoS ONE (2009)

Bottom Line: One of these proteins, SMU.440, has very few homologs in the current protein databases and it does not fall into any protein functional families.The co-occurrence of a MarR protein within the same operon among these oral pathogens suggests that SMU.440 may be associated with antibiotic resistance.From the interlinking structural and bioinformatics studies, we have concluded that SMU.440 could be involved in polyketide-like antibiotic resistance, providing a better understanding of this hypothetical protein.

View Article: PubMed Central - PubMed

Affiliation: National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, Beijing, People's Republic of China.

ABSTRACT
As an oral bacterial pathogen, Streptococcus mutans has been known as the aetiologic agent of human dental caries. Among a total of 1960 identified proteins within the genome of this organism, there are about 500 without any known functions. One of these proteins, SMU.440, has very few homologs in the current protein databases and it does not fall into any protein functional families. Phylogenetic studies showed that SMU.440 is related to a particular ecological niche and conserved specifically in some oral pathogens, due to lateral gene transfer. The co-occurrence of a MarR protein within the same operon among these oral pathogens suggests that SMU.440 may be associated with antibiotic resistance. The structure determination of SMU.440 revealed that it shares the same fold and a similar pocket as polyketide cyclases, which indicated that it is very likely to bind some polyketide-like molecules. From the interlinking structural and bioinformatics studies, we have concluded that SMU.440 could be involved in polyketide-like antibiotic resistance, providing a better understanding of this hypothetical protein. Besides, the combination of multiple methods in this study can be used as a general approach for functional studies of a protein with unknown function.

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Related in: MedlinePlus

Crystal structure of SMU.440.(A) Overall structure of SMU.440 in cartoon representation. (B) SMU.440 homodimer has a twofold symmetry, the axis of which is indicated in black opal shape.
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pone-0007245-g003: Crystal structure of SMU.440.(A) Overall structure of SMU.440 in cartoon representation. (B) SMU.440 homodimer has a twofold symmetry, the axis of which is indicated in black opal shape.

Mentions: SMU.440 is comprised of three α-helices and a seven-stranded antiparallel β-sheet, bending into an unclosed β-barrel (Fig. 3A). The structure belongs to the SCOP superfamily of Bet v1-like [21] proteins. There are two molecules per asymmetric unit (ASU) and they form a homodimer via a pair of antiparallel β-strands (Fig. 3B). The dimer has a twofold symmetry, with the twofold axis in the center of the dimer interface and perpendicular to the plane of the extended β-sheet of the dimer. Prediction of assemblies by the PISA server [22] indicates that this dimer interface is the largest (interface area 946.6 Å2) with a favorable interaction energy (ΔiG −6.9 kcal/mol), in agreement with the dimer state in solution observed during the gel filtration chromatography experiment. However, it is not clear if there is any functional advantage associated with the dimerization.


Bioinformatics and structural characterization of a hypothetical protein from Streptococcus mutans: implication of antibiotic resistance.

Nan J, Brostromer E, Liu XY, Kristensen O, Su XD - PLoS ONE (2009)

Crystal structure of SMU.440.(A) Overall structure of SMU.440 in cartoon representation. (B) SMU.440 homodimer has a twofold symmetry, the axis of which is indicated in black opal shape.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2749211&req=5

pone-0007245-g003: Crystal structure of SMU.440.(A) Overall structure of SMU.440 in cartoon representation. (B) SMU.440 homodimer has a twofold symmetry, the axis of which is indicated in black opal shape.
Mentions: SMU.440 is comprised of three α-helices and a seven-stranded antiparallel β-sheet, bending into an unclosed β-barrel (Fig. 3A). The structure belongs to the SCOP superfamily of Bet v1-like [21] proteins. There are two molecules per asymmetric unit (ASU) and they form a homodimer via a pair of antiparallel β-strands (Fig. 3B). The dimer has a twofold symmetry, with the twofold axis in the center of the dimer interface and perpendicular to the plane of the extended β-sheet of the dimer. Prediction of assemblies by the PISA server [22] indicates that this dimer interface is the largest (interface area 946.6 Å2) with a favorable interaction energy (ΔiG −6.9 kcal/mol), in agreement with the dimer state in solution observed during the gel filtration chromatography experiment. However, it is not clear if there is any functional advantage associated with the dimerization.

Bottom Line: One of these proteins, SMU.440, has very few homologs in the current protein databases and it does not fall into any protein functional families.The co-occurrence of a MarR protein within the same operon among these oral pathogens suggests that SMU.440 may be associated with antibiotic resistance.From the interlinking structural and bioinformatics studies, we have concluded that SMU.440 could be involved in polyketide-like antibiotic resistance, providing a better understanding of this hypothetical protein.

View Article: PubMed Central - PubMed

Affiliation: National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, Beijing, People's Republic of China.

ABSTRACT
As an oral bacterial pathogen, Streptococcus mutans has been known as the aetiologic agent of human dental caries. Among a total of 1960 identified proteins within the genome of this organism, there are about 500 without any known functions. One of these proteins, SMU.440, has very few homologs in the current protein databases and it does not fall into any protein functional families. Phylogenetic studies showed that SMU.440 is related to a particular ecological niche and conserved specifically in some oral pathogens, due to lateral gene transfer. The co-occurrence of a MarR protein within the same operon among these oral pathogens suggests that SMU.440 may be associated with antibiotic resistance. The structure determination of SMU.440 revealed that it shares the same fold and a similar pocket as polyketide cyclases, which indicated that it is very likely to bind some polyketide-like molecules. From the interlinking structural and bioinformatics studies, we have concluded that SMU.440 could be involved in polyketide-like antibiotic resistance, providing a better understanding of this hypothetical protein. Besides, the combination of multiple methods in this study can be used as a general approach for functional studies of a protein with unknown function.

Show MeSH
Related in: MedlinePlus