1. MYCOBACTERIUM TUBERCULOSIS PROTEOME 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

2. 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

3. 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)

13. 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

21. Venn diagram of InterPro hits for the 3 organisms E.coli M.tuberB. sub 675 68125 62 129 76 59 Protein secretion system Flagellar proteins Gram -ve porins Lypolytic enzymes Specific transposases PE/PPE proteins Disease resistance protein Cytochrome B5 Specific transposases Tet resistance protein Spore proteins Staph nuclease Pectate lyase Differences: -Glycosol hydrolases -Proteases -Transcription factors -Transporters -Oxygenases

22. Pie charts of whole proteome analysis of 4 organisms

23. Distribution of protein functions