The first structure for a member of the DUF3349 (PF11829) family of protein, 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 a-helices a1 (M1 - Y16), a2 (P21 - C33), a3 (S37 - G52), a4 (G58 - H65) and a5 (S72 - G87) held together by a largely conserved group of hydrophobic amino acid side chains. Heteronuclear steady-state {1H)-15N NOE values indicate an overall structure that is rigid on the picosecond timescale. The thermal stability of Rv0543c characterized by circular dichroism spectroscopy indicates that Rv0543c irreversibly unfolds upon heating with a melting temperature of ~64ºC. While the biological function of Rv0543c is still unknown, the presence of DUF3349 proteins predominately 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.
Revised: February 1, 2011 |
Published: January 25, 2011
Citation
Buchko G.W., I. Phan, P.J. Myler, T.C. Terwilliger, and C.Y. Kim. 2011.Inaugural structure from the DUF3349 superfamily of proteins, Mycobacterium tuberculosis Rv0543c.Archives of Biochemistry and Biophysics 506, no. 2:150-156. PNWD-SA-9015. doi:10.1016/j.abb.2010.12.001