The structure of a resuscitation-promoting factor domain from Mycobacterium tuberculosis shows homology to lysozymes

Resuscitation-promoting factor (RPF) proteins reactivate stationary-phase cultures of (G+C)-rich Gram-positive bacteria including the causative agent of tuberculosis, Mycobacterium tuberculosis. We report the solution structure of the RPF domain from M. tuberculosis Rv1009 (RpfB) solved by heteronuclear multidimensional NMR. Structural homology with various glycoside hydrolases suggested that RpfB cleaved oligosaccharides. Biochemical studies indicate that a conserved active site glutamate is important for resuscitation activity. These data, as well as the presence of a clear binding pocket for a large molecule, indicate that oligosaccharide cleavage is probably the signal for revival from dormancy

RpfC (Rv1884) atomic structure shows high structural conservation within the resuscitation promoting factor catalytic domain

We report the first structure of the catalytic domain of RpfC (Rv1884), one of theresuscitation-promoting factors (RPFs) from Mycobacterium tuberculosis. The structure was solved using molecular replacement, once the space group had been correctly identified as twinned P21 rather than the apparent C2221 by searching for anomalous scattering sites in P1. The structure displays a very high degree of structural conservation with the structures of the catalytic domains of RpfB (Rv1009) and RpfE (Rv2450) already published. This structural conservation highlights the importance of the versatile domain composition of the RPF family

Antimicrobial treatment improves mycobacterial survival in nonpermissive growth conditions

Antimicrobials targeting cell wall biosynthesis are generally considered inactive against nonreplicating bacteria. Paradoxically, we found that under nonpermissive growth conditions, exposure of Mycobacterium bovis BCG bacilli to such antimicrobials enhanced their survival. We identified a transcriptional regulator, RaaS (for regulator of antimicrobial-assisted survival), encoded by bcg1279 (rv1219c) as being responsible for the observed phenomenon. Induction of this transcriptional regulator resulted in reduced expression of specific ATP-dependent efflux pumps and promoted long-term survival of mycobacteria, while its deletion accelerated bacterial death under nonpermissive growth conditions in vitro and during macrophage or mouse infection. These findings have implications for the design of antimicrobial drug combination therapies for persistent infectious diseases, such as tuberculosis

Etudes structurales de la protéine Maba (FabG1), une b-cétoacyl-ACP réductase de Mycobacterium tuberculosis. Une cible pour la conception de nouveaux antituberculeux

MONTPELLIER-BU Sciences (341722106) / SudocSudocFranceF

Equivalence between Euler angle conventions for the description of tensorial interactions in liquid NMR: application to different software programs

International audienceLong-range orientational restraints derived from alignment or rotational diffusion tensors have greatly contributed to the expansion of applications in biomolecular NMR. The orientation of the principal axis system of these tensors is usually described by the so-called Euler angles. However, no clear consensus has emerged concerning the convention of the associated orthogonal rotations. As a result, the different programs that derive or predict them have adopted different conventions, which make comparison between their results difficult. Moreover, the rotation schemes are seldom completely described. Here, we summarize the different conventions, determine which ones are adopted by commonly used software packages, and establish the formal equivalencies between the different calculated Euler angles

Mycobacterium tuberculosis S-adenosyl-l-homocysteine hydrolase is negatively regulated by Ser/Thr phosphorylation

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A novel mode of regulation of the Staphylococcus aureus Vancomycin-resistance-associated response regulator VraR mediated by Stk1 protein phosphorylation

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Crystal Structure of MabA from Mycobacterium tuberculosis, a Reductase involved in Long-chain Fatty Acid Biosynthesis

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Dynamic and structural characterization of a bacterial FHA protein reveals a new autoinhibition mechanism.

International audienceThe OdhI protein is key regulator of the TCA cycle in Corynebacterium glutamicum. This highly conserved protein is found in GC rich Gram-positive bacteria (e.g., the pathogenic Mycobacterium tuberculosis). The unphosphorylated form of OdhI inhibits the OdhA protein, a key enzyme of the TCA cycle, whereas the phosphorylated form is inactive. OdhI is predicted to be mainly a single FHA domain, a module that mediates protein-protein interaction through binding of phosphothreonine peptides, with a disordered N-terminal extension substrate of the serine/threonine protein kinases. In this study, we solved the solution structure of the unphosphorylated and phosphorylated isoforms of the protein. We observed a major conformational change between the two forms characterized by the binding of the phosphorylated N-terminal part of the protein to its own FHA domain, consequently inhibiting it. This structural observation corresponds to a new autoinhibition mechanism described for a FHA domain protein