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The PE-PPE domain in mycobacterium reveals a serine α/β hydrolase fold and function: an in-silico analysis.

Sultana R, Tanneeru K, Guruprasad L - PLoS ONE (2011)

Bottom Line: The structure comprises a lid insertion with a closed structure conformation and has a solvent inaccessible active site.The oxyanion hole that stabilizes the negative charge on the tetrahedral intermediate has been identified.These results provide the directions for the design of experiments to establish the function of PE and PPE proteins.

View Article: PubMed Central - PubMed

Affiliation: School of Chemistry, University of Hyderabad, Hyderabad, India.

ABSTRACT
The PE and PPE proteins first reported in the genome sequence of Mycobacterium tuberculosis strain H37Rv are now identified in all mycobacterial species. The PE-PPE domain (Pfam ID: PF08237) is a 225 amino acid residue conserved region located towards the C-terminus of some PE and PPE proteins and hypothetical proteins. Our in-silico sequence analysis revealed that this domain is present in all Mycobacteria, some Rhodococcus and Nocardia farcinica genomes. This domain comprises a pentapeptide sequence motif GxSxG/S at the N-terminus and conserved amino acid residues Ser, Asp and His that constitute a catalytic triad characteristic of lipase, esterase and cutinase activity. The fold prediction and comparative modeling of the 3-D structure of the PE-PPE domain revealed a "serine α/β hydrolase" structure with a central β-sheet flanked by α-helices on either side. The structure comprises a lid insertion with a closed structure conformation and has a solvent inaccessible active site. The oxyanion hole that stabilizes the negative charge on the tetrahedral intermediate has been identified. Our findings add to the growing list of serine hydrolases in mycobacterium, which are essential for the maintenance of their impermeable cell wall and virulence. These results provide the directions for the design of experiments to establish the function of PE and PPE proteins.

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Related in: MedlinePlus

Domain architecture of proteins in M. tuberculosis strain H37Rv genome comprising the PE-PPE domain that encodes a serine hydrolase.
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pone-0016745-g001: Domain architecture of proteins in M. tuberculosis strain H37Rv genome comprising the PE-PPE domain that encodes a serine hydrolase.

Mentions: The PSI-BLAST searches identified that the PE-PPE domain is present in all mycobacterial genomes. In M. tuberculosis H37Rv strain, ten proteins comprise the PE-PPE domain. The domain architecture of these proteins is shown in Figure 1. The detailed genome-wide sequence analysis revealed that homologs of PE and PPE proteins (Rv0151c, Rv0152c, Rv0159c, Rv0160c, Rv1430, Rv1800, Rv2608, Rv3539) are present in M. tuberculosis, M. bovis, M. kansasii, M. marinum and M. ulcerans genomes. The homologs of hypothetical proteins (Rv1184c and Rv3822) that comprise only the PE-PPE domain are present in M. tuberculosis, M. bovis, M. parascrofulaceum, M. smegmatis, M. vanbaalenii, M. abscessus, M. avium, M. leprae and Mycobacterium sp. JLS, KMS and MCS. The list of proteins comprising the PE-PPE domain in mycobacterial genomes is shown in Table S1. Further, we also observed that the homologs of the hypothetical proteins are present in Nocardia farcinica (YP_120155.1) and some species from Rhodococcus (YP_002767666.1, YP_002764179.1, YP_002783136.1, YP_002781243.1, YP_705817.1, ZP_04388076.1, ZP_04387701.1, ADD80824.1) that belong to actinobacteria but these genomes do not comprise the PE and PPE family proteins.


The PE-PPE domain in mycobacterium reveals a serine α/β hydrolase fold and function: an in-silico analysis.

Sultana R, Tanneeru K, Guruprasad L - PLoS ONE (2011)

Domain architecture of proteins in M. tuberculosis strain H37Rv genome comprising the PE-PPE domain that encodes a serine hydrolase.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3037379&req=5

pone-0016745-g001: Domain architecture of proteins in M. tuberculosis strain H37Rv genome comprising the PE-PPE domain that encodes a serine hydrolase.
Mentions: The PSI-BLAST searches identified that the PE-PPE domain is present in all mycobacterial genomes. In M. tuberculosis H37Rv strain, ten proteins comprise the PE-PPE domain. The domain architecture of these proteins is shown in Figure 1. The detailed genome-wide sequence analysis revealed that homologs of PE and PPE proteins (Rv0151c, Rv0152c, Rv0159c, Rv0160c, Rv1430, Rv1800, Rv2608, Rv3539) are present in M. tuberculosis, M. bovis, M. kansasii, M. marinum and M. ulcerans genomes. The homologs of hypothetical proteins (Rv1184c and Rv3822) that comprise only the PE-PPE domain are present in M. tuberculosis, M. bovis, M. parascrofulaceum, M. smegmatis, M. vanbaalenii, M. abscessus, M. avium, M. leprae and Mycobacterium sp. JLS, KMS and MCS. The list of proteins comprising the PE-PPE domain in mycobacterial genomes is shown in Table S1. Further, we also observed that the homologs of the hypothetical proteins are present in Nocardia farcinica (YP_120155.1) and some species from Rhodococcus (YP_002767666.1, YP_002764179.1, YP_002783136.1, YP_002781243.1, YP_705817.1, ZP_04388076.1, ZP_04387701.1, ADD80824.1) that belong to actinobacteria but these genomes do not comprise the PE and PPE family proteins.

Bottom Line: The structure comprises a lid insertion with a closed structure conformation and has a solvent inaccessible active site.The oxyanion hole that stabilizes the negative charge on the tetrahedral intermediate has been identified.These results provide the directions for the design of experiments to establish the function of PE and PPE proteins.

View Article: PubMed Central - PubMed

Affiliation: School of Chemistry, University of Hyderabad, Hyderabad, India.

ABSTRACT
The PE and PPE proteins first reported in the genome sequence of Mycobacterium tuberculosis strain H37Rv are now identified in all mycobacterial species. The PE-PPE domain (Pfam ID: PF08237) is a 225 amino acid residue conserved region located towards the C-terminus of some PE and PPE proteins and hypothetical proteins. Our in-silico sequence analysis revealed that this domain is present in all Mycobacteria, some Rhodococcus and Nocardia farcinica genomes. This domain comprises a pentapeptide sequence motif GxSxG/S at the N-terminus and conserved amino acid residues Ser, Asp and His that constitute a catalytic triad characteristic of lipase, esterase and cutinase activity. The fold prediction and comparative modeling of the 3-D structure of the PE-PPE domain revealed a "serine α/β hydrolase" structure with a central β-sheet flanked by α-helices on either side. The structure comprises a lid insertion with a closed structure conformation and has a solvent inaccessible active site. The oxyanion hole that stabilizes the negative charge on the tetrahedral intermediate has been identified. Our findings add to the growing list of serine hydrolases in mycobacterium, which are essential for the maintenance of their impermeable cell wall and virulence. These results provide the directions for the design of experiments to establish the function of PE and PPE proteins.

Show MeSH
Related in: MedlinePlus