Structural study on MRA1997 protein from Mycobacterium tuberculosis by NMR spectroscopy

Abstract

About one third of the worlds population is infected with Mycobacterium tuberculosisand 15 % of those infected can occur disease. Even though several antibiotic drugs were discovered, multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) have increasingly emerged. Now, it is significance to study the genetic and physiology of M. tuberculosis to improve strategies for new drugs discovery. The study which determine the structures of hypothetical proteins and identify their functions may find outthe virulence factors, new bacterial targets. And then, they can be used for designing new drugs by SBDD (Structure Based Drug Discovery) technique. In here, we predicted the structure and function of a hypothetical protein, MRA1997 from M. tuberculosis by NMR spectroscopy. NMR backbone and side-chain assignments determined that MRA1997 consists of a three-stranded antiparallel β-sheet, two α-helices and some loops through CS23D program. Many structural homolog proteins of MRA1997function as a transcription initiation factor.Especially, the β-strands regionassociates with DNA binding. NMR protein-DNA titration showed several peaks corresponding to the amino acids of β-stands in MRA1997 were perturbed. It suggests that MRA1997 may have the DNA binding properties. This study will be useful in future studies on a refined 3D structure after NOE assignment and a function of transcription initiator.