A mutant of Escherichia coli resistant to serine hydroxamate which has a large increase in Km for serine of seryl-tRNA synthetase is described. The mutant serS gene was cloned and sequenced and was found to contain a single-base-pair mutation, resulting in the substitution of the residue alanine 262 by valine in motif 2. The methyl side chain of alanine 262 is not exposed at the active site, an...

Growing evidence shows that hydroxamate-based compounds exhibit broad-spectrum pharmacological properties including anti-tumor activity. However, the precise mechanisms underlying hydroxamate derivative-induced cancer cell death remain incomplete understood. In this study, we explored the anti-tumor mechanisms of a novel aliphatic hydroxamate-based compound, WMJ-J-09, in FaDu head and neck squa...

One alternative method for drug delivery involves the use of siderophore-antibiotic conjugates. These compounds represent a specific means by which potent antimicrobial agents, covalently linked to iron-chelating siderophores, can be actively transported across the outer membrane of gram-negative bacteria. These "Trojan Horse" antibiotics may prove useful as an efficient means to combat multi-d...

The release of iron from ferritin by aceto- and benzohydroxamic acids was studied at two different iron chelator concentrations (100 and 10 mM), at two pH values (7.4 and 5.2), and in the presence or absence of urea. Collectively, the results demonstrate that both aceto- and benzohydroxamic acids remove iron from ferritin. Aceto- and benzohydroxamic acids penetrate the ferritin shell and react ...

Threonyl transfer ribonucleic acid synthetase from Escherichio coli was purified 320-fold in 10% yield. The K, for the over-all reaction, in which threonyl-tRNA is formed, is 1O-4 M for ATP and 12 X 1OM6 M for threonine. The molecular weight is 117,000 + 9% as determined by sucrose density gradient centrifugation. The enzyme readily catalyzes a threonine-dependent ATP-PP; exchange reaction. Thr...

In the Bacillus subtilis mutant 1D-4, the hydroxamate Desferal inhibited growth, iron uptake, and deoxyribonucleic acid synthesis but did not quantitatively affect synthesis of ribonucleic acid and protein.

Novel citrate-hydroxamate siderophores, named nannochelins A, B and C, were isolated from the culture broth of the myxobacterium Nannocystis exedens strain Na e485. The new substances showed weak growth-inhibitory activity against some bacteria and fungi.

The phosphorylated intermediate in the (Na + K)-activated adenosine triphosphatase (Na-K ATPase) has been characterized as an L-glutamyl-gamma-phosphate residue in the enzyme. This has been accomplished by digestion of the phosphorylated and nonphosphorylated forms of the enzyme with pepsin, reaction of the pepsin digests with [2,3-(3)H]N-(n-propyl)hydroxylmine, further digestion of the derivat...

Staphylococcus aureus is a human pathogen causing globally significant morbidity and mortality. The development of antibiotic resistance in S. aureus highlights the need for a preventive vaccine. In the present paper we explore the structure and function of FhuD2 (ferric-hydroxamate uptake D2), a staphylococcal surface lipoprotein mediating iron uptake during invasive infection, recently descri...

The first reaction in protein biosynthesis has been presumed to be the interaction of ATP, amino acid, and enzyme (amino acid-activating enzyme, aminoacyl transfer RNA ligase, tRNA synthetase) to form an enzyme-bound aminoacyl adenylic anhydride. Such aminoacyl anhydrides could react forward with hydroxylamine or with tRNA or backward with [““PI-PPi. Experiments, primarily involving inhibitors,...