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

Classification of hypothetical proteins Q10401 PEPTIDASE B (EC ). IPR Cytosol aminopeptidase O33261 L-ASPARAGINE PERMEASE. IPR Amino acid permease Q11018 HYPOTHETICAL ABC TRANSPORTER. IPR ABC transporters family P96936 HYPOTHETICAL 54.8 KD PROTEIN. IPR Aminoacyl-transfer RNA synthetases class-II P96255 ACETATE KINASE (EC ). IPR Acetate and butyrate kinase Q10535 HYPOTHETICAL PROTEIN RV0873. IPR Acyl-CoA dehydrogenase Q10974 PROBABLE THIOESTERASE RV2928 (EC ). IPR Thioesterase Q50705 ALANINE RACEMASE (EC ). IPR Alanine racemase Q11024 HYPOTHETICAL 67.7 KD PROTEIN. IPR Domain of unknown function P71571 HYPOTHETICAL 83.6 KD PROTEIN. IPR ATP-dependent DNA ligase Q50720 HYPOTHETICAL 20.6 KD PROTEIN RV3405C. IPR Bacterial regulatory proteins, TetR M. tuberculosis proteome = 3784 proteins 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 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 E.coli M.tuberB. sub 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

Pie charts of whole proteome analysis of 4 organisms

Distribution of protein functions