Antibiotics crystal structures

The X-ray crystal structures of many of these complexes have now been determined representative examples are. shown in Fig. 4.11 from which it is clear that, at least for the larger cations, coordinative saturation and bond rhrectionality are far less significant factors than in many transition element complexes. Further interest in these ligands stems from their use in biochemical modelling since they sometimes mimic the behaviour of naturally occurring, neutral, macrocydic antibiotics such as valinomycin, monactin, nonactin, nigericin... 

The third current approach is synthesis of peptide chains as models for the helical peptaibol (Section 8.2) and gramicidin (Section 8.3) ion channels. Considerable work has been carried out in the former area, involving synthesis of Aib-containing small peptides, in order to obtain conformational data applicable to the more complex oligopeptide antibiotics. By working with such fragments it has been possible to obtain valuable X-ray crystal structure information on the helical conformation of ala-methin 246), emerimicin 247), suzukacillin 248), and other members of the peptaibol series. 

Brufani M, Cellai L, Cerrini S, Fedeli W, Marchi E, Segre A, Vaciago A X-ray crystal structure of 4-deoxy-3 -bromopyrido[l, 2 -l,2]imidazo[5,4-c]rifamycin SV. J Antibiot (Tokyo) 1984 37 1623-1627. 

The symmetrical ring enniatin (304) forms a potassium complex (Figure 9.3) whose crystal structure indicates that the cation is contained in the macrocyclic cavity and is coordinated by the six carbonyl oxygen atoms which are orientated such that three lie above and three lie below the main plane of the molecule (Dobler, Dunitz Krajewski, 1969). Apart from those just discussed, it needs to be noted that a range of other structures of antibiotic molecules and their metal complexes have been determined (Hilgenfeld Saenger, 1982). 

The first structures of this kind were reported in 1993 pectate lyase G from Erwinia chrysanthemi (Yoder et al, 1993) and alkaline protease from Pseudomonas aeruginosa (Baumann et al, 1993). Based on consideration of these crystal structures, the term parallel //-helix was introduced for a fold containing three //-strands per coil, and parallel //-roll for a fold with two //-strands per coil (Baumann etal, 1993 Yoder andjurnak, 1995 Yoder et al., 1993). The epithet parallel was intended to emphasize the distinction between these folds and the previously observed helical structure of the antibiotic gramicidin which contains both l- and D-amino acids and... 

Structural steels, tellurium in, 24 425 Structure(s), see also Chain structure Chemical structures Cocontinuous structures Controlled structure Crystal structure Molecular structure Morphology Phase structure of carbon fibers, 26 737-739 detersive systems for, 8 413t HDPE, 20 157-162 LLDPE, 20 182-184, 203-205 polyesterether elastomer, 20 72-73 polyester fiber, 20 21 polyether antibiotics, 20 137-139 polyimide, 20 276-278 polymer, 20 395-405 protein, 20 449 PTT, 20 68t... 

Ramakrishnan and co-workers 3-A crystal structures of two different aminoglycosides (paromomycin and streptomycin) bound to the 30S subunit laid to rest much of the debate concerning the binding mode of aminoglycoside antibiotics. Paromomycin was found bound to the major groove of helix 44 (H44), confirming mutagenesis studies that had been carried out previously. ... 

A feature of these acidic antibiotics is that their chemical constitutions were established by crystal structure analysis, having defied classical organic chemistry, even aided by spectroscopic techniques. The reason for this is apparent from the formulae, (X)—(XII), examples chosen because the heavy atom salts are isomorphous with those of alkali metals. The formulae show the correct absolute configurations as determined by X-ray methods. 

Although the acidic antibiotics do not show the high selectivity characteristic of the neutral ones, there is still some preference, a strong one for monovalent as compared with divalent cations, and within the monovalent cations a variation from one acid to another. Monensin prefers sodium to potassium. The larger nigeridn, (X7), prefers potassium to sodium its silver, potassium, and sodium salts are isomorphous and anhydrous. Crystal structure determinations on the silver salt were carried out independently by workers in the U.S.A. (78) and in Japan... 

A quite new type of antibiotic and one of the few naturally-occurring boron compounds is boromycin (86). Hydrolytic cleavage of D-valine with the M(7) hydroxides gave caesium and rubidium salts of this antibiotic, and crystal structure analysis established the formula as (XIIT). The rubidium ion is irregularly coordinated by eight oxygen atoms. Experiments with models showed that the cation site would be the natural place for the—NH3+ end of the D-valine residue, and the whole structure raises the possibility that transport of larger alkali metals is related to the N-ends of peptides and proteins. 

Table 1. X-ray crystal structures of complexes of alkali cation carrier antibiotics (53)... 

Although numerous models of the interactions between the qulnoxaline antibiotics and IMA have been proposed, no definitive conclusion about the precise Banner of the interactions could be made (46). Recently, the crystal structure of a synthetic analog of triostin A, des-N-tetramethyltriostin A (TdNlMH) (47). has been determined. A naturally occurlng quinoline-containing antibiotic,luzopeptin,has been purified and characterized and its three dimensional structure determined (48). 

When mechanism is understood, mechanism-based inhibitors such as transition state analogues and suicide inhibitors (Section 3.4) may also be designed. Recent determination of the crystal structure of a complex of penicillin G with a deacylation-defective mutant /3-lactamase from E. coli shows how such antibiotics are recognized and how they are destroyed (Strynadka et al., 1992). 

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