Adenylyltransferase, modification

Structures of several important aminoglycoside antibiotics. Ring II is 2-deoxystreptamine. The resemblance between kanamycin and amikacin and between gentamicin, netilmicin, and tobramycin can be seen. The circled numerals on the kanamycin molecule indicate points of attack of plasmid-mediated bacterial transferase enzymes that can inactivate this drug. , , and , acetyltransferase , phosphotransferase , adenylyltransferase. Amikacin is resistant to modification at , , , and . 

M FIGURE 22-7 Second level of regulation of glutamine synthetase covalent modifications, (a) An adenylylated Tyr residue, (b) Cascade leading to adenylylation (inactivation) of glutamine synthetase. AT represents adenylyltransferase UT, uridylyltransferase. Details of this cascade are discussed in the text. 

Superimposed on the allosteric regulation is inhibition by adenylylation of (addition of AMP to) Tyr , located near the enzyme s active site (Fig. 22-7). This covalent modification increases sensitivity to the allosteric inhibitors, and activity decreases as more subunits are adenylylated. Both adenylylation and deadenylylation are promoted by adenylyltransferase (AT in Fig. 

Glutamine synthetase can be covalently modified by the attachment of an AMP to each of its 12 subunits. The more adenylylated the enzyme becomes, the more susceptible it is to feedback inhibition by the compounds listed in question 21. Thus, covalent modification modulates the sensitivity of the enzyme to its effectors. An added level of control exists in this system adenylyltransferase, the enzyme that adenylylates glutamine synthetase, is itself covalently modified. 

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