Antibiotic binding

Although most /3- lactam antibiotics bind covalently to some or all of the same six proteins, there are decided differences among them in terms of their relative affinities. For example, cefoxitin (see Table 1 for structures) fails to bind to protein 2 while cephacetrile binds very slowly to proteins 5 and 6. Cephaloridine binds most avidly to protein 1, the transpeptidase, and inhibits cell elongation and causes lysis at its minimum inhibitory concentration. On the other hand, cephalexin binds preferentially to protein 3 and causes inhibition of cell division and filament formation (75PNA2999, 77MI51002). 

The ribosome is the cellular target of a large and chemically diverse group of antibiotics. The antibiotic binding sites are clustered at functional centers of the ribosome and the majority are composed exclusively of RNA. The drugs interfere with the positioning and movement of substrates, products and ribosomal components that are essential for protein synthesis. 

NMR structures also reveal that rings I and II of both antibiotics bind in a similar orientation with respect to the RNA, direct the specific interaction with... 

Screening of microbial products has led to the discovery of a number of growth-inhibiting compounds that have proved to be clinically useful in cancer chemotherapy. Many of these antibiotics bind to DNA through intercalation between specific bases and block the synthesis of RNA, DNA, or both cause DNA strand scission and interfere with cell replication. All of the anticancer antibiotics now being used in clinical practice are products of various strains of the soil microbe Streptomyces. These include the anthracyclines, bleomycin, and mitomycin. 

The binding of the various RNAP subunits, repressors, and activators has been studied using mutant promoter sequences,31 37 antibiotic-binding sites,50 51... 

The monohactams, like pcncillins and cephalosporins, interfere with the synthesis of bacterial cell walls. /l-Lactani antibiotics bind to a series of penicillin-binding proteins (PBPs) on the cytoplasmic membrane and their antibacterial effect is believed to result from inhibition of a subset of these PBPs known as peplidoglycan transpeptidases. 

It is also known that a given P-lactam antibiotic binds to only a certain number of PBPs, and affinities of PBPs for P-lactam antibiotics vary greatly [1,2,25,58], Therefore, a PBP that binds specifically to a given p-lactam can in principle be purified using an affinity column containing this p-lactam. Altema-... 

The observation of selective complexation shifts in the nucleic acid resonances of the synthetic DNA demonstrate a change in the glycosidic torsion angles of the adenosine and thymidine residues and a minimal perturbation in the base pair overlaps on addition of netropsin. These structural perturbations at the antibiotic binding site are propagated to adjacent antibiotic-free base pair regions at low netropsin concentrations. 

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