Structure-Function Studies of the Staphylococcal Methicillin Resistance Antirepressor MecR2

Arede, Pedro; Botelho, Tiago O.; Guevara, Tibisay; Usón, Isabel; Oliveira, Duarte C.; Gomis‐Rüth, F. Xavier

doi:10.1074/jbc.m112.448134

Cited by 4 publications

(3 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with the presence of a DNA-binding domain, MecR2 shows strong but nonspecific DNA-binding activity. This activity contributes to the expression of methicillin resistance; a deletion mutant in this domain shows significantly diminished antirepressor activity (93). Likewise, a MecR2 mutant in which an 11-residue stretch in the intermediate scaffold domain was replaced by 4 glycine residues also had reduced antirepressor activity, suggesting that this domain is also relevant to the function of MecR2 (93).…”

Section: Regulation Of Methicillin Resistancementioning

confidence: 96%

“…Cotranscribed from the mecR1 promoter along with mecR1 and mecI, mecR2 encodes an antirepressor that binds MecI, disrupting its binding to the mecA promoter and facilitating its proteolysis (92). This proteolysis of MecI, independent of MecR1 and therefore presumed to occur through native cytosolic proteases, is essential for optimal methicillin resistance; expression of a proteolytic resistant MecI decreases methicillin resistance (81 MecR2 has been resolved, revealing that MecR2 is structurally similar to the ROK (repressors, open reading frames, and kinases) protein family and that it comprises three domains, an N-terminal DNA-binding-like domain and a C-terminal dimerization domain separated by an intermediate scaffold domain (Figure 5) (93). Consistent with the presence of a DNA-binding domain, MecR2 shows strong but nonspecific DNA-binding activity.…”

Section: Regulation Of Methicillin Resistancementioning

confidence: 98%

See 1 more Smart Citation

Mechanisms of Methicillin Resistance in Staphylococcus aureus

Peacock

Paterson

2015

Annu. Rev. Biochem.

500

371

View full text Add to dashboard Cite

Staphylococcus aureus is a major human and veterinary pathogen worldwide. Methicillin-resistant S. aureus (MRSA) poses a significant and enduring problem to the treatment of infection by such strains. Resistance is usually conferred by the acquisition of a nonnative gene encoding a penicillin-binding protein (PBP2a), with significantly lower affinity for β-lactams. This resistance allows cell-wall biosynthesis, the target of β-lactams, to continue even in the presence of typically inhibitory concentrations of antibiotic. PBP2a is encoded by the mecA gene, which is carried on a distinct mobile genetic element (SCCmec), the expression of which is controlled through a proteolytic signal transduction pathway comprising a sensor protein (MecR1) and a repressor (MecI). Many of the molecular and biochemical mechanisms underlying methicillin resistance in S. aureus have been elucidated, including regulatory events and the structure of key proteins. Here we review recent advances in this area.

show abstract

Section: Regulation Of Methicillin Resistancementioning

confidence: 96%

Section: Regulation Of Methicillin Resistancementioning

confidence: 98%

Mechanisms of Methicillin Resistance in Staphylococcus aureus

Peacock

Paterson

2015

Annu. Rev. Biochem.

500

371

View full text Add to dashboard Cite

show abstract

“…The catalytically active sugar kinases with an N-terminal ATP-binding motif are well studied, regarding tertiary structure [ 3 – 5 ], substrate specificity [ 6 , 7 ] and biochemistry [ 8 , 9 ]. Recently, some ROK-family regulators containing an N-terminal helix-turn-helix DNA-binding motif have been investigated [ 10 – 12 ]. In 2005, the first structure of a ROK-family regulator, the global regulator of sugar metabolism Mlc from Escherichia coli , was solved [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Characterization of DNA Binding Sites of RokB, a ROK-Family Regulator from Streptomyces coelicolor Reveals the RokB Regulon

2016

View full text Add to dashboard Cite

ROK-family proteins have been described to act either as sugar kinases or as transcriptional regulators. Few ROK-family regulators have been characterized so far and most of them are involved in carbon catabolite repression. RokB (Sco6115) has originally been identified in a DNA-affinity capturing approach as a possible regulator of the heterologously expressed novobiocin biosynthetic gene cluster in Streptomyces coelicolor M512. Interestingly, both, the rokB deletion mutants as well as its overexpressing mutants showed significantly reduced novobiocin production in the host strain S.coelicolor M512. We identified the DNA-binding site for RokB in the promoter region of the novobiocin biosynthetic genes novH-novW. It overlaps with the novH start codon which may explain the reduction of novobiocin production caused by overexpression of rokB. Bioinformatic screening coupled with surface plasmon resonance based interaction studies resulted in the discovery of five RokB binding sites within the genome of S. coelicolor. Using the genomic binding sites, a consensus motif for RokB was calculated, which differs slightly from previously determined binding motifs for ROK-family regulators. The annotations of the possible members of the so defined RokB regulon gave hints that RokB might be involved in amino acid metabolism and transport. This hypothesis was supported by feeding experiments with casamino acids and L-tyrosine, which could also explain the reduced novobiocin production in the deletion mutants.

show abstract

Homology modeling, vasorelaxant and bradykinin-potentiating activities of a novel hypotensin found in the scorpion venom from Tityus stigmurus

Machado

G.M.

Monteiro

et al. 2015

Toxicon

View full text Add to dashboard Cite

In a recent work by our group involving a transcriptomics approach applied to the venom glands from Tityus stigmurus we identified a new family of peptides called Hypotensins (TSTI0006C) (Almeida et al., 2012). The cluster TSTI0006C was analyzed in the main 25 amino acid residues and named T. stigmurus Hypotensin (TistH), showing a molecular mass of 2.7 kDa, an absence of cysteines and the presence of two C-terminal proline residues, which are a bradykinin-potentiating peptide (BPP) signature. Here, we describe the homology modeling of the three-dimensional structure of TistH. In addition, we evaluated the cardiovascular effects elicited by TistH in normotensive rats. Firstly, TistH showed no cytotoxic effect on horse erythrocyte. Furthermore, in normotensive rats TistH was able to potentiate the hypotensive action of bradykinin (BK) and induced a vasorelaxant effect in mesenteric artery rings by endothelium-dependent release of nitric oxide (NO) and demonstrated independent inhibition of angiotensin converting enzyme (ACE). Our data can contribute to a better understanding of the structural and functional characteristics of TistH and suggest its potential use in cardiovascular diseases.

show abstract

Structure-Function Studies of the Staphylococcal Methicillin Resistance Antirepressor MecR2

Cited by 4 publications

References 78 publications

Mechanisms of Methicillin Resistance in Staphylococcus aureus

Mechanisms of Methicillin Resistance in Staphylococcus aureus

Characterization of DNA Binding Sites of RokB, a ROK-Family Regulator from Streptomyces coelicolor Reveals the RokB Regulon

Homology modeling, vasorelaxant and bradykinin-potentiating activities of a novel hypotensin found in the scorpion venom from Tityus stigmurus

Contact Info

Product

Resources

About