Transglycosylase

IB 90,000 250 (8) transglycosylase, major transpeptidase of cell elongation essential for cylindrical cell wall synthesis rapid lysis... 

Proteins identified by their ability to bind labelled (3-lactam antibiotics in vivo and in vitro. The intrinsic activities of PBPs include transglycosylase/transpepti-dase, carboxypeptidase and endopeptidase activities required for the formation of the bacterial murein sacculus forming the bacterial cell wall. The enzymes are located in the cytoplasmic membrane. 

Brenk R, Meyer EA, Reuter K, Stubbs MT, Garcia GA, Diederich E, Klebe G. Crystallographic study of inhibitors of tRNA-guanine transglycosylase snggests a new structure-based pharmacophore for virtual screening. J Mol Biol 2004 338 55-75. 

PUA Putative RNA-binding domain in PseudoUridine synthase and Archaeosine transglycosylase E(MFP)AB 5(5) 3(3) ... 

The reason that the cyclodextrin transglycosylase occurs only in Bacillus macerans and a few other thermophilic bacteria has not, as yet, been determined. Nevertheless, it is interesting to speculate about the possible evolutionary advantage that a bacterium might have by possessing the cyclodextrin transglycosylase. Because the cyclodextrins have no end... 

Fig. 4.6 Example for successful structure-based virtual screening to identify submicromolar tRNA-guanine transglycosylase (TGT) inhibitors based on X-ray structures ofweaker ligands.

Synthesis. The synthases are present at the endomembrane system of the cell and have been isolated on membrane fractions prepared from the cells (5,6). The nucleoside diphosphate sugars which are used by the synthases are formed in the cytoplasm, and usually the epimerases and the other enzymes (e.g., dehydrogenases and decarboxylases) which interconvert them are also soluble and probably occur in the cytoplasm (14). Nevertheless some epimerases are membrane bound and this may be important for the regulation of the synthases which use the different epimers in a heteropolysaccharide. This is especially significant because the availability of the donor compounds at the site of the transglycosylases (the synthases) is of obvious importance for control of the synthesis. The synthases are located at the lumen side of the membrane and the nucleoside diphosphate sugars must therefore cross the membrane in order to take part in the reaction. Modulation of this transport mechanism is an obvious point for the control not only for the rate of synthesis but for the type of synthesis which occurs in the particular lumen of the membrane system. Obviously the synthase cannot function unless the donor molecule is transported to its active site and the transporters may only be present at certain regions within the endomembrane system. It has been observed that when intact cells are fed radioactive monosaccharides which will form and label polysaccharides, these cannot always be found at all the membrane sites within the cell where the synthase activities are known to occur (15). A possible reason for this difference may be the selection of precursors by the transport mechanism. 

It is likely that in addition to the synthases and epimerases there is also present at the membrane in close proximity to these, transporter systems for the transfer of the nucleoside diphosphate donor compounds to the transglycosylases situated on the lumen side of the membrane. 

In addition to transpeptidases, other penicillin-binding proteins (PBPs) function as transglycosylases and carboxypeptidases. All of the PBPs are involved with assembly, maintenance, or regulation of peptidoglycan cell wall synthesis. When (3-lactam antibiotics inactivate PBPs, the consequence to the bacterium is a structurally weakened cell wall, aberrant morphological form, cell lysis, and death. 

Bulgecins were reported for the first time in 1982 [158]. Their structures, such as (94), were established soon afterwards [159, 160] and they were found to interfere with the cell-wall synthesis of gram-negative bacteria due to a unique mechanism inhibiting vital bacterial Soluble Lytic Transglycosylase (SLT) [161]. 

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