抗生素作用机制（英文PPT）Antibioticsthat Inhibit Cell Wall .ppt

A pentaglycine linker is added to the disaccharide. In the case of S. aureus the linker is added to the Lys residue which is the third a.a. in the pentapeptide. These glycines will inevitably be involved in the cross-linking of the peptidoglycan chains. The five glycines are donated by t-RNA, BUT ribosomes do not participate. This now represents the completed disaccharide. The disaccharide is now added to an acceptor, which is the glycan chain. The result is that the glycan chain becomes two units longer. The enzyme responsible is called peptidoglycan synthetase. This reaction is inhibited by VANCOMYCIN, which binds to the terminal D-ala-D-ala region to prevent glycan chain growth. The other product is the pyrophosphate form of the phospholipid carrier. To complete the cycle, the phospholipid carrier must be returned to its original form. BACITRACIN prevents cleavage of the pyrophosphate group and thus halts the cycle. Repeated turns of the cycle produce a long chain that is OUTSIDE the membrane. This slide aims to solidify for you the structure of the disaccharide units that form the peptidoglycan chain. The residue on the left is N-ac-muramic acid; that on the right is N-ac-glucosamine. Links ultimately will go from the Lys in the 3-position on one unit to the Ala in the 4-position on another, mediated by the pentaglycine linker, which is attached to the Lys. Again, the structure shown is for S. aureus. The linker is a region in which gram+ and gram- bacteria differ. [NOTE: in E. coli there is no pentaglycine linker and the a.a. in position 3 is m-diaminopimelate.] Stage 3: Cross-linking of the peptidoglycan chains to form essentially one large molecule, outside the bacterial cell, that completely encapsulates it. Stage 3: Cross-linking of the peptidoglycan chains to form essentially one large molecule, outside the bacterial cell, that completely encapsulates it. Topic 2: Drug resistance. Decreased antibiotic effectiveness is emerging as a major m