Your SlideShare is downloading. ×
Au bio tlya
Au bio tlya
Au bio tlya
Au bio tlya
Au bio tlya
Au bio tlya
Au bio tlya
Au bio tlya
Au bio tlya
Au bio tlya
Au bio tlya
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×
Saving this for later? Get the SlideShare app to save on your phone or tablet. Read anywhere, anytime – even offline.
Text the download link to your phone
Standard text messaging rates apply
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total Views
36
On Slideshare
0
From Embeds
0
Number of Embeds
1
Actions
Shares
0
Downloads
0
Comments
0
Likes
0
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
No notes for slide

Transcript

  • 1. Molecular modeling and in silico characterization of Mycobacterium tuberculosis TlyA: Possible misannotation of this tubercle bacilli-hemolysin Yakovlev Pavel St-Petersburg Academic University RAS April 27, 2013
  • 2. Background Tuberculosis is an infectious disease that mainly afflicts populations in third-world countries. Although most infected people will never develop an active form of the disease, the global TB death rate is substantial, being around two million people per year. The situation has been further exacerbated by the emergence and spread of extremely resistant Mycobacterium tuberculosis strains (XDR) which, together with the lack of effective antibiotics, urges the development of new alternatives for controlling this worldwide public health threat. Consequently, most research efforts have focused on understanding M. tuberculosis biology with the aim of identifying new therapeutic and vaccine targets. Yakovlev Pavel Molecular modeling and in silico characterization 2/11
  • 3. Motivation The TlyA protein has a controversial function as a virulence factor in Mycobacterium tuberculosis. There is no evidence however for TlyA relevance in the survival of tubercle bacilli inside host cells or whether both ctivities are functionally linked. Yakovlev Pavel Molecular modeling and in silico characterization 3/11
  • 4. Pre-modeling research Homology BLAST results: TlyA homologs are found mainly in prokariotic organisms TlyA homologs are also present in eukariotic organisms (plats and algae) Yakovlev Pavel Molecular modeling and in silico characterization 4/11
  • 5. Mycobacterium homologs Yakovlev Pavel Molecular modeling and in silico characterization 5/11
  • 6. Pre-modeling research Transcriptional units TlyA is a product of the IprJ-recN operon. All other gene products, except for tlyA, are involved in intermediary metabolism, cell wall biosynthesis and signal transduction rather than virulence. Green - cell wall synthesis Red - signal transduction Brown - evolutionarily conserved Yellow - intermediary metabolism Other: pseudogenes, PE/PPE and IS/phages Yakovlev Pavel Molecular modeling and in silico characterization 6/11
  • 7. Modeling The three-dimensional structure of a putative hemolysin from Streptococcus thermophilus was used as template for homology modeling. identity (37.2%,RMSD 0.44 ˚A, E-value 4.7e-26) domain architecture was similar to TlyA proteins The obtained parameters suggested that the selected hemolysin structure was a suitable template for TlyA Yakovlev Pavel Molecular modeling and in silico characterization 7/11
  • 8. Modeling Result PMDB: PM0076044 Tool: UCSF Chimera Yakovlev Pavel Molecular modeling and in silico characterization 8/11
  • 9. Results Yakovlev Pavel Molecular modeling and in silico characterization 9/11
  • 10. Results In silico curation suggested that TlyA is involved in ribosomal biogenesis and that there is a functional annotation error regarding this protein family in several microbial and plant genomes, including the M. tuberculosis genome. This in silico structure analysis of M. tuberculosis proteins allowed a deeper understanding of TlyA’s function and challenges the initially described function of TlyArelated proteins. Rather than its hypothetical function as a hemolysin, our data suggested functions as an MTase based on in silico prediction. Yakovlev Pavel Molecular modeling and in silico characterization 10/11
  • 11. Q&A Thank you for your attention! Q&A Yakovlev Pavel Molecular modeling and in silico characterization 11/11

×