Bacterial ribosomal protein

Pharmacology Nitrofurantoin is bactericidal in urine at therapeutic doses. Nitrofurantoin is reduced by bacterial flavoproteins to reactive intermediates that inactivate or alter bacterial ribosomal proteins and other macromolecules. Pharmacokinetics ... 

Inactivates bacterial ribosomal proteins leading to a loss of vital processes of synthesizing proteins, DNA, RNA, and cell wall. Also leads to the loss of aerobic energy metabolism. It has been around since the 1950s without serious emergence of resistance because of its broad-based range of modes of action. 

Summary. We recently developed an all-atom free energy force field (PFFOl) for protein structure prediction with stochastic optimization methods. We demonstrated that PFFOl correctly predicts the native conformation of several proteins as the global optimum of the free energy surface. Here we review recent folding studies, which permitted the reproducible all-atom folding of the 20 amino-acid trp-cage protein, the 40-amino acid three-helix HIV accessory protein and the sixty amino acid bacterial ribosomal protein L20 with a variety of stochastic optimization methods. These results demonstrate that all-atom protein folding can be achieved with present day computational resources for proteins of moderate size. 

Figure 1. Overlay of the native(red) and folded (blue) structures of trp-cage protein [35], the HIV accessory protein [13] and the bacterial ribosomal protein L20 [14],...

Nitrofurantoin works by inactivating bacterial ribosomal proteins and other large molecules and has a bactericidal effect. The drug is concentrated in the urine and relies on adequate renal function (glomerular filtration rate (GFR) >30 mL/min) to guarantee activity. Nitrofurantoin is ineffective for upper UTI because it does not achieve adequate concentrations in the blood. The use of nitrofurantoin in patients with moderate-to-severe renal failure (GFR <50 mL/min) is not recommended due to increased risk of peripheral neuropathy (Kucers et ah, 1997). 

Makarova KS, Ponomarev VA, Koonin EV Two C or not two C recurrent disruption of Zn-ribbons, gene duplication, lineage-specific gene loss, and horizontal gene transfer in evolution of bacterial ribosomal proteins, [http // genomebiology.eom/2001/2/9/research/0033] webcite Genome Biol 2001, 2(9) RESEARCH 0033. 

Mechanism of Action. THie earliest studies on the mechanism of action of lincomycin showed that lincomycin had the immediate effect on Staphjlococcus aureus of complete inhibition of protein synthesis (23). TThis inhibition results from the blocking of the peptidyltransferase site of the SOS subunit of the bacterial ribosome (24). Litde effect on DNA and RNA synthesis was observed. 

Ribosomes in bacteria and in the mitochondria of higher eukaryotic cells differ from the mammalian ribosome described in Ghapter 35. The bacterial ribosome is smaller (70S rather than SOS) and has a different, somewhat simpler complement of RNA and protein... 

Of the fonr possible optical isomers of chloramphenicol, only the o-threo form is active. This antibiotic selectively inhibits protein synthesis in bacterial ribosomes by binding to the 50S subunit in the region of the A site involving the 23 S rRNA. The normal binding of the aminoacyl-tRNA in the A site is affected by chloramphenicol in such a... 

Approximately 90% to 95% of whole-cell MALDI MS profiles are representative of the ribosomal proteins abundant in rapid growth whole cells. Although the identification of proteins, from whole bacterial cells, by MALDI-TOF MS analysis is ambiguous, at best, due to the low-mass accuracy and resolving power, several researchers realized that many of the observed... 

Although ribosomal proteins are readily observed as in Figures 13.7 and 13.8 altered matrix conditions can alter the relative ionization of bacterial whole-cell compounds. A systematic analysis involving laser power/fluence and sample preparation conditions reveals that if the concentrated trifluo-roacetic acid is added and the laser power increased above optimal conditions, ionization of bacterial surface compounds can be enhanced. Figure 13.9 is the resulting 9.4 T MALDI-FTMS, seen are both the Braun s lipoprotein56,57 and the Murein lipoprotein. Both of these compounds are complex combinations of hydrocarbon lipids attached to a protein base. This is the first MALDI-FTMS observation of surface proteins desorbed directly from whole cells by influencing ionization conditions. 

Kenner, R. A. and Aboderin, A. A. (1971). A new fluorescent probe for protein and nucleoprotein conformation. Binding of 7-(p-Methoxyben-zylamino) -4-nitrobenzoxadiazole to bovine trypsinogen and bacterial ribosomes. Biochemistry 10, 4433 1440. 

Tetracyclines are a group of antibiotics derived from bacteria. Chlortet-racycline was isolated from Streptomyces aureofaciens and oxytetracycline from Streptomyces rimosus. Tetracychnes act by binding to receptors on the bacterial ribosome and inhibit bacterial protein synthesis. 

Dahopristin binds to bacterial ribosome and inhibits protein synthesis. 

Newer and more generally usefnl macrolide antibiotics include azithromycin (Zithromax) and clarithromycin (Biaxin). These too are wide-spectrum antibiotics and both are semisynthetic derivatives of erythromycin. Like the tetracyclines, the macrolide antibiotics act as protein synthesis inhibitors and also do so by binding specifically to the bacterial ribosome, thongh at a site distinct from that of the tetracyclines. 

Linezohd (Zyvox) is an oxazolidinone, a tive-membered heterocychc ring that forms the core of the hnezohd structure. The approval of hnezohd by the FDA in 2000 marked the first new structural class of antibacterial introduced into medical practice in the United States in 40 years. It is notable for its activity against methicillin-resistant Staph aureus, MRSA, and vancomycin-resistant Enterococcus faecium, VRE. It is bacteriostatic rather than bactericidal but finds significant use in patients with an intact immune system. Like several other classes of antibacterials, linezolid is an inhibitor of protein synthesis. It interacts specifically with the RNA component of a bacterial ribosome subunit to prevent initiation of protein synthesis. 

Pharmacology Lincomycin and clindamycin, known collectively as lincosamides, bind exclusively to the 50 S subunit of bacterial ribosomes and suppress protein synthesis. Cross-resistance has been demonstrated between these 2 agents. Clindamycin is preferred because it is better absorbed and more potent. Pharmacokinetics Administration with food markedly impairs lincomycin (but not clindamycin) oral absorption. 

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