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 3.-.-.-). IPR000819 Cytosol aminopeptidaseO33261 L-ASPARAGINE PERMEASE. IPR002027 Amino acid permeaseQ11018 HYPOTHETICAL ABC TRANSPORTER. IPR001617 ABC transporters familyP96936 HYPOTHETICAL 54.8 KD PROTEIN. IPR002106 Aminoacyl-transfer RNA synthetases class-IIP96255 ACETATE KINASE (EC 2.7.2.1). IPR000890 Acetate and butyrate kinaseQ10535 HYPOTHETICAL PROTEIN RV0873. IPR001552 Acyl-CoA dehydrogenaseQ10974 PROBABLE THIOESTERASE RV2928 (EC 3.1.2.-). IPR001031 ThioesteraseQ50705 ALANINE RACEMASE (EC 5.1.1.1). IPR000821 Alanine racemaseQ11024 HYPOTHETICAL 67.7 KD PROTEIN. IPR001633 Domain of unknown function P71571 HYPOTHETICAL 83.6 KD PROTEIN. IPR000977 ATP-dependent DNA ligaseQ50720 HYPOTHETICAL 20.6 KD PROTEIN RV3405C. IPR001647 Bacterial regulatory proteins, TetRM. 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

E.coli

M.tuberB. sub

675

68125

62

129

76

59

Protein secretion systemFlagellar proteinsGram -ve porinsLypolytic enzymesSpecific transposases

PE/PPE proteinsDisease resistance proteinCytochrome B5Specific transposases

Tet resistance proteinSpore proteinsStaph nucleasePectate lyase

Differences:

-Glycosol hydrolases-Proteases-Transcription factors-Transporters-Oxygenases

Pie charts of whole proteome analysis of 4 organisms

Distribution of protein functions

Met

abol

ism

Reg

ulat

ion

DN

A/R

NA

met

abol

ism

Cel

l cyc

le

Def

ense

/Pat

hoge

nesi

s

Stru

ctur

al

Mis

cella

neou

s

Pro

tein

fold

ing/

degr

adat

ion

Sig

nal t

rans

duct

ion

Tran

spor

t

Unk

now

n

M. tuberculosisE. coli

B. subtilisS. cerevisae0

5

10

15

20

25

M. tuberculosis

E. coli

B. subtilis

S. cerevisae