title: Enriching the annotation of Mycobacterium tuberculosis H37Rv proteome using remote homology detection approaches: insights into structure and function.
abstract: The availability of the genome sequence of Mycobacterium tuberculosis H37Rv has encouraged determination of large numbers of protein structures and detailed definition of the biological information encoded therein; yet, the functions of many proteins in M. tuberculosis remain unknown. The emergence of multidrug resistant strains makes it a priority to exploit recent advances in homology recognition and structure prediction to re-analyse its gene products. Here we report the structural and functional characterization of gene products encoded in the M. tuberculosis genome, with the help of sensitive profile-based remote homology search and fold recognition algorithms resulting in an enhanced annotation of the proteome where 95% of the M. tuberculosis proteins were identified wholly or partly with information on structure or function. New information includes association of 244 proteins with 205 domain families and a separate set of new association of folds to 64 proteins. Extending structural information across uncharacterized protein families represented in the M. tuberculosis proteome, by determining superfamily relationships between families of known and unknown structures, has contributed to an enhancement in the knowledge of structural content. In retrospect, such superfamily relationships have facilitated recognition of probable structure and/or function for several uncharacterized protein families, eventually aiding recognition of probable functions for homologous proteins corresponding to such families. Gene products unique to mycobacteria for which no functions could be identified are 183. Of these 18 were determined to be M. tuberculosis specific. Such pathogen-specific proteins are speculated to harbour virulence factors required for pathogenesis. A re-annotated proteome of M. tuberculosis, with greater completeness of annotated proteins and domain assigned regions, provides a valuable basis for experimental endeavours designed to obtain a better understanding of pathogenesis and to accelerate the process of drug target discovery.
authors.affiliation: Indian Institute of Science Mathematics Initiative, Indian Institute of Science, Bangalore 560012, India; Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India. Electronic address: rgayatri@mbu.iisc.ernet.in.
authors.forename: Gayatri
authors.initials: G
authors.lastname: Ramakrishnan
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK. Electronic address: bernardo@cryst.bioc.cam.ac.uk.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Ochoa-Montaño
authors.affiliation: National Centre for Biological Sciences, Tata Institute of Fundamental Research, Gandhi Krishi Vignyan Kendra Campus, Bangalore 560065, India. Electronic address: upadhyayulas@ncbs.res.in.
authors.forename: Upadhyayula S
authors.initials: US
authors.lastname: Raghavender
authors.affiliation: Indian Institute of Science Mathematics Initiative, Indian Institute of Science, Bangalore 560012, India; Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India. Electronic address: rmudgal@mbu.iisc.ernet.in.
authors.forename: Richa
authors.initials: R
authors.lastname: Mudgal
authors.affiliation: National Centre for Biological Sciences, Tata Institute of Fundamental Research, Gandhi Krishi Vignyan Kendra Campus, Bangalore 560065, India; Manipal University, Manipal, Karnataka 576104, India. Electronic address: adwait@ncbs.res.in.
authors.forename: Adwait G
authors.initials: AG
authors.lastname: Joshi
authors.affiliation: Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India. Electronic address: nchandra@biochem.iisc.ernet.in.
authors.forename: Nagasuma R
authors.initials: NR
authors.lastname: Chandra
authors.affiliation: National Centre for Biological Sciences, Tata Institute of Fundamental Research, Gandhi Krishi Vignyan Kendra Campus, Bangalore 560065, India. Electronic address: mini@ncbs.res.in.
authors.forename: Ramanathan
authors.initials: R
authors.lastname: Sowdhamini
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK. Electronic address: tlb20@cam.ac.uk.
authors.forename: Tom L
authors.initials: TL
authors.lastname: Blundell
authors.affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India. Electronic address: ns@mbu.iisc.ernet.in.
authors.forename: Narayanaswamy
authors.initials: N
authors.lastname: Srinivasan
mesh_terms: D006867:Hydrolases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary; D020543:Proteome / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D020539:Sequence Analysis, Protein / Q000379:methods; D040681:Structural Homology, Protein
chemical_list: D020543:Proteome; D006867:Hydrolases; C527647:HsaD protein, Mycobacterium tuberculosis
keywords: Mycobacterium tuberculosis; Protein annotation; Remote homology detection; Sequence analysis