Pathways of Enzymatic Phosphotransfer Reactions |
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Authors: | P A Frey E Cardemil R Iyengar J Van Pelt |
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Institution: | Institute for Enzyme Research, Graduate School, and Department of Biochemistry , College of Agricultural and Life Sciences, University of Wisconsin-Madison , Madison , Wisconsin , 53705 , U.S.A. |
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Abstract: | Abstract Mevalonate 5-pyrophosphate (MVAPP) decarboxylase catalyzes the decarboxylation of MVAPP to isopentenyl pyro-phosphate, an ATP-dependent process in which 3-phospho-MVAPP is a transient intermediate that undergoes concomitant decarboxylation and elimination of phosphate. Reaction of (Sp)-adenosine 5′-0-3-thio 3-17O 2,180] triphosphate in place of ATP produces (R)-17O,18O] thiophosphate in place of phosphate. Therefore, the phosphotransfer step producing 3-phospho-MVAPP proceeds with inversion of configuration at P. Gentamicin nucleotidyl-transferase catalyzes the reaction of ATP with the C-2″ hydroxyl group of aminoglycoside antibiotics to produce AMP-2″-aminoglycosides, thereby inactivating the drugs. Enzymatic reaction of (Sp)-2′-deoxyadenosine 5′-Oα-17O] triphosphate with tobramycin produces (Rp)-α-17O]dAMP-2″-tobramycin. Therefore, transfer of the 2′-deoxyadenosine 5′-phosphoryl group proceeds with inversion of configuration. Since both reactions are uncomplicated bisubstrate processes and both proceed with inversion at P, it is likely that both proceed by mechanisms involving direct, single-step phosphotransfer from the phospho-donor substrate to the acceptor, rather than by double-displacement mechanisms involving covalent, phosphoenzyme-intermediates. |
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