title: Inaugural structure from the DUF3349 superfamily of proteins, Mycobacterium tuberculosis Rv0543c.
abstract: The first structure for a member of the DUF3349 (PF11829) family of proteins, Rv0543c from Mycobacterium tuberculosis, has been determined using NMR-based methods and some of its biophysical properties characterized. Rv0543c is a 100 residue, 11.3 kDa protein that both size exclusion chromatography and NMR spectroscopy show to be a monomer in solution. The structure of the protein consists of a bundle of five α-helices, α1 (M1-Y16), α2 (P21-C33), α3 (S37-G52), α4 (G58-H65) and α5 (S72-G87), held together by a largely conserved group of hydrophobic amino acid side chains. Heteronuclear steady-state {¹H}-¹⁵N NOE, T₁, and T₂ values are similar through-out the sequence indicating that the backbones of the five helices are in a single motional regime. The thermal stability of Rv0543c, characterized by circular dichroism spectroscopy, indicates that Rv0543c irreversibly unfolds upon heating with an estimated melting temperature of 62.5 °C. While the biological function of Rv0543c is still unknown, the presence of DUF3349 proteins predominantly in Mycobacterium and Rhodococcus bacterial species suggests that Rv0543 may have a biological function unique to these bacteria, and consequently, may prove to be an attractive drug target to combat tuberculosis.
authors.affiliation: Biological Sciences Division and Seattle Structural Genomics Center for Infectious Disease, Pacific Northwest National Laboratory, Richland, WA 99352, USA. garry.buchko@pnl.gov
authors.forename: Garry W
authors.initials: GW
authors.lastname: Buchko
authors.forename: Isabelle
authors.initials: I
authors.lastname: Phan
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Myler
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Terwilliger
authors.forename: Chang-Yub
authors.initials: CY
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D055592:Biophysical Phenomena; D002942:Circular Dichroism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000737:chemistry* / Q000235:genetics; D019906:Nuclear Magnetic Resonance, Biomolecular; D055550:Protein Stability; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity; D040681:Structural Homology, Protein
chemical_list: D001426:Bacterial Proteins; D011994:Recombinant Proteins