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D A Scogin

Publications and source records attributed to D A Scogin.

3 recordsLinked to original sources
PubMed1983

Studies on the complex formed between bacitracin A and divalent cations.

Bacitracin A is a peptide antibiotic which forms stoichiometric complexes with divalent cations, including Ni2+ and Zn2+. In this paper it is shown that the metal-bacitracin complex contains a group which has a pKa near pH 5.5. Deprotonation of the group is concomitant with the aggregation and precipitation of the metal-bacitracin complex. Bacitracin A, in the absence of metals, does not contain any group which has a pKa in this range. It is postulated that this group is the N-terminal amino of isoleucine, which was previously postulated not to be directly involved in metal coordination based on proton release measurements. An attempt was made to demonstrate directly that the N-terminal amino group is not coordinated to the metal by examining the reactivity of this group with 2,4,6-trinitrobenzene sulfonate. It was clearly shown that bound metals protect the N-terminal amino group from reacting with this reagent. It is speculated that this metal-protection results from a combination of factors, including steric hindrance.

Bacitracin↗
PubMed1980

Binding of nickel and zinc ions to bacitracin A.

Bacitracin A is a cyclic dodecapeptide antibiotic produced by Bacillus licheniformis. Bacteriocidal activity requires the presence of divalent cations such as Zn2+. The metal-bacitracin A complex binds to bactoprenyl pyrophosphate, a lipid intermediate required for cell wall biosynsthesis which is found within the bacterial membrane. In this paper, the pH dependence of the metal binding to bacitracin A is investigated in an effort to define the sites of metal coordination. Most of the studies described in this report were performed with Ni2+ and Zn2+. Metal binding was monitored by observing changes in the ultraviolet absorption spectrum of bacitracin A and by monitoring the proton release which is concomitant with metal binding to the peptide. It was determined that both Ni2+ and Zn2+ form 1:1 complexes with bacitracin A in solution. These complexes are soluble in acidic solutions, but above approximately pH 5.5 they become insoluble. On the basis of the data reported as well as results previously reported from other laboratories, a model for divalent metal ion binding to bacitracin is suggested. It is proposed that the metal coordinates directly to the glutamate carboxyl, the histidine imidazole, and the thiazoline ring. The aspartate carboxyl and N-terminal amino group are not directly involved in metal binding. It is further proposed that due to the proximity of the metab, the pK of the N-terminal amino is shifted from 7.7 to 5.7 upon metal binding. Deprotonation of this group is suggested to cause precipitation of the bacitracin A-metal complex. This model is consistent with all the metal binding data and, furthermore, is consistent with the 1H NMR data presented in the accompanying paper [Mosberg, H. I., Scogin, D. A., Storm, D. R., & Gennis, R. B. (1980) Biochemistry (following paper in this issue)].

Bacitracin↗