Transcript No Slide Title

MYCOBACTERIUM
TUBERCULOSIS PROTEOME
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M. tuberculosis- intracellular pathogen
- TB prevalent in Africa and Asia
- 1/3 population is infected
- 8 million new cases per year
Complete sequence is available in SPTR:
NCBI_TaxID=1773 (Rv=83332) (CDC1551=83331)
4087 proteins in SPTR, 2706 are “hypothetical”
66% of proteins in SPTR uncharacterised
Classification of hypothetical proteins
Q10401 PEPTIDASE B (EC 3.-.-.-). IPR000819 Cytosol aminopeptidase
O33261 L-ASPARAGINE PERMEASE. IPR002027 Amino acid permease
Q11018 HYPOTHETICAL ABC TRANSPORTER. IPR001617 ABC transporters family
P96936 HYPOTHETICAL 54.8 KD PROTEIN. IPR002106 Aminoacyl-transfer RNA synthetases class-II
P96255 ACETATE KINASE (EC 2.7.2.1). IPR000890 Acetate and butyrate kinase
Q10535 HYPOTHETICAL PROTEIN RV0873. IPR001552 Acyl-CoA dehydrogenase
Q10974 PROBABLE THIOESTERASE RV2928 (EC 3.1.2.-). IPR001031 Thioesterase
Q50705 ALANINE RACEMASE (EC 5.1.1.1). IPR000821 Alanine racemase
Q11024 HYPOTHETICAL 67.7 KD PROTEIN. IPR001633 Domain of unknown function
P71571 HYPOTHETICAL 83.6 KD PROTEIN. IPR000977 ATP-dependent DNA ligase
Q50720 HYPOTHETICAL 20.6 KD PROTEIN RV3405C. IPR001647 Bacterial regulatory proteins, TetR
M. tuberculosis proteome = 3784 proteins
- 2505 have InterPro matches (64.7%)
- Of those in InterPro, at least 860 hypothetical can be characterised
- 33% of hypothetical proteins in SPTR, or 22% proteome
Proteome analysis of Mtb
• Extensive gene duplication, functional redundancy and
diversification
• Precise function 40%, some functional info 44%, 16%
unknown, probably Mycobacterial specific
• 9% genome encodes PE and PPE proteins (gly rich)
• Many fatty acid metabolism proteins >250 cf 50 in E.coli
(reflection of cell wall)
• Has two hemoglobins for oxygen storage
• Mycobactins for iron
• Glyoxylate shunt NB for latency or persistence (isocitrate
lyase)
Structural information
• 1079 ORFs can be assigned to SCOP -1566
domains, 1639 regions
• 482 (12.4%) have hits in HSSP
• 9 (0.2%) have hits in PDB
Venn diagram of InterPro hits for the
3 organisms
Differences:
E.coli
-Glycosol hydrolases
-Proteases
-Transcription factors
-Transporters
-Oxygenases
Protein secretion system
Flagellar proteins
Gram -ve porins
Lypolytic enzymes
Specific transposases
129
125
68
675
B. sub
76
62
Tet resistance protein
Spore proteins
Staph nuclease
Pectate lyase
59
M.tuber
PE/PPE proteins
Disease resistance
protein
Cytochrome B5
Specific transposases
Pie charts of whole proteome analysis of 4
organisms
Unknown
Transport
Signal transduction
Protein folding/degradation
Miscellaneous
Structural
Defense/Pathogenesis
Cell cycle
DNA/RNA metabolism
Regulation
Metabolism
Distribution of protein
functions
25
20
15
M. tuberculosis
10
E. coli
B. subtilis
S. cerevisae
5
0
S. cerevisae
B. subtilis
E. coli
M. tuberculosis