Membranverankerung und Intervesikel-Transfer eines Derivats des Antibiotikums Moenomycin A

Anikin, Alexej; Buchynskyy, Andrij; Kempin, Uwe; Stembera, Katka; Welzel, Peter; Lantzsch, Gabriela

doi:10.1002/(sici)1521-3757(19991216)111:24<3931::aid-ange3931>3.3.co;2-b

Cited by 3 publications

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“…The moenomycins rather inhibit the transglycosylase by interacting with the enzyme ( E. coli PBP1b) reversibly. , The structural similarities between the moenomycins and both the glycosyl donor and the glycosyl acceptor of the transglycosylation reaction are obvious (see Figure ). From structure−activity relationships it has been concluded that the moenomycins first bind to the cyctoplasmic membrane via their lipid moiety and that membrane anchoring is an essential step preceding the highly selective binding of the sugar part to the donor binding site of the enzyme. The structural features that are known to be responsible for the antibiotic activity are indicated by arrows in formula 141 (Figure ).…”

Section: Moenomycinsmentioning

confidence: 99%

Syntheses around the Transglycosylation Step in Peptidoglycan Biosynthesis

Welzel

2005

Chem. Rev.

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Section: Moenomycinsmentioning

confidence: 99%

Syntheses around the Transglycosylation Step in Peptidoglycan Biosynthesis

Welzel

2005

Chem. Rev.

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“…Moenomycin A (1) binds reversibly to E. coli PBP 1b [1]. From structure-activity relationships [3] [4], it has been inferred that the moenomycins, after unselective anchoring to the cytoplasmic membrane via their lipid moiety (for a discussion, see [5]), bind highly selectively via their carbohydrate part to the donor binding subsites of the enzyme. The structural features that are known to be responsible for the antibiotic activity are indicated by full arrows in 2 [3] [4].…”

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confidence: 99%

Studies on the Synthesis of Trisaccharide Analogues of the Antibiotic Moenomycin A

Yang

Hennig

Findeisen

et al. 2004

Helvetica Chimica Acta

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“…Moenomycin A (2) has been demonstrated to bind reversibly to E. coli PBP 1b [1]. From structure-activity relationships [10] [11], it has been concluded that the moenomycins, after unselective anchoring to the cytoplasmic membrane via their lipid moiety (for a discussion, see [12]), bind highly selectively via their carbohydrate part to the donor-binding subsites of the enzyme. The structural features that are known to be responsible for the antibiotic activity are indicated by arrows in 1 (see Fig.…”

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“…The minimum inhibitory concentration (MIC) values against seven different Staph. aureus strains (ATCC 25923, ATCC 29213, MRSA 1309, SG 511, PEG 18, PEG 5, and KNS PEG 5) were determined by a serial twofold micro-dilution method on microtiter plates as described previously [12]. All compounds displayed strong antibiotic activity, albeit weaker than that of moenomycin A itself [35] ( Table 1).…”

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On Penicillin‐Binding Protein 1b Affinity‐Labeling Reagents

Volke

Daghish

Hennig

et al. 2003

Helvetica Chimica Acta

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Dedicated to Professor Duilio Arigoni on the occasion of his 75th birthdayThe synthesis of some 3-aryl-3-(trifluoromethyl)3H-diazirine and benzophenone-based photoaffinity labels is reported. The photolabile group is bound to a scaffold that also accommodates functional groups to which an indicator unit (biotin) and the bioactive ligand can be attached orthogonally. To three of the labels, moenomycin was conjugated with the aim to provide tools for the identification of the moenomycin binding site within the transglycosylase domain of the enzyme PBP 1b. Some preliminary photoaffinity-labeling experiments were carried out.Introduction. ± Peptidoglycan is an essential cell-wall constituent of almost all eubacteria. It is a heteropolymer consisting of glycan strands cross-linked via short peptide chains. The final events of peptidoglycan biosynthesis at the outside of the cytoplasmic membrane are the formation of the macromolecular architecture by two major types of reaction, i) formation of the polysaccharide strands (transglycosylation) and ii) formation of peptide cross-linkages between the glycan chains (transpeptidation) (for review, see [1]). A representation of the transition state of the transglycosylation reaction is shown in Fig. 1, a [2]. Both the glycosyl donor (the growing peptidoglycan chain) and the glycosyl acceptor (the disaccharide-derived lipid II) (see [1]) are attached to the outer face of the cytoplasmic membrane via a C 55 anchor. The transglycosylation reaction is catalyzed by a number of multimodular bifunctional polymerases (that catalyze also the transpeptidation reaction) designated as class-A high-molecular-mass penicillin-binding proteins (PBPs). Of these, PBP 1b from Escherichia coli has been studied in great detail [3]. It comprises 844 amino acid residues and contains a short cytosolic N-terminus, a membrane span, the D198-G435 glycosyl-transferase module, and the Q447-N844 acyl-transferase module. Within the glycosyl-transferase module, Glu233 has been shown to be central to the transglycosylation, and, in the active site of the acyl transferase, Ser510 is essential, the acylation of which forms the basis of the antibiotic properties of the b-lactams. Recently, the soluble extracellular region of PBP 1b from Streptococcus pneumoniae has been expressed and characterized biochemically [4]. From the most-recent kinetic characterization of the E. coli PBP 1b, it was deduced that a doubly charged metal ion bound to the diphosphate group assists departure of the leaving group, whereas the essential Glu233 acts as a base, removing the proton from the 4-OH group of the glycosyl acceptor (see Fig. 1, a) [5].

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Membranverankerung und Intervesikel-Transfer eines Derivats des Antibiotikums Moenomycin A

Cited by 3 publications

References 0 publications

Syntheses around the Transglycosylation Step in Peptidoglycan Biosynthesis

Syntheses around the Transglycosylation Step in Peptidoglycan Biosynthesis

Studies on the Synthesis of Trisaccharide Analogues of the Antibiotic Moenomycin A

On Penicillin‐Binding Protein 1b Affinity‐Labeling Reagents

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