Fig. 10 | The Journal of Antibiotics

Fig. 10

From: Targeting adenylate-forming enzymes with designed sulfonyladenosine inhibitors

Fig. 10

Biochemistry of YrdC-like carbamoyltransferases. a In t6A biosynthesis, TsaC/YrdC converts threonine (10.1) to N-carboxythreonine (10.2), then adenylates it to form a TC-AMP intermediate (10.3). A separate enzyme, TsaD/Kae1, condenses the adenylate with the 6-amino group of tRNA-A37 to form t6A (10.4). b In [NiFe]-hydrogenase maturation, the multidomain protein HypF carries out AP-domain-catalyzed hydrolysis of carbamoylphosphate (10.5) to carbamic acid (10.6), YrdC-like domain-catalyzed adenylation to form a carbamoyl-AMP intermediate (10.7) and Kae1-like domain-catalyzed condensation with the C-terminal Cys-351 side-chain thiol nucleophile of HypE to form an S-thiocarbamate intermediate (10.8). Downstream enzymes then catalyze dehydration to a thiocyanate intermediate (10.9), cyanide transfer to an iron center, and installation of the complex in the [NiFe]-hydrogenase active site (10.10, X = bridging ligand). c The natural product tobramycin (10.11) is O-carbamoylated by TobZ, which contains YrdC-like and Kae1-like domains, to form nebramycin 5′ (10.12). HypE structure derived from PDB ID: 3VTI [84]; [NiFe]-hydrogenase structure derived from PDB ID: 2FRV [217]. AP acyl phosphatase domain, t6A 6-N-(threon-2-N-ylcarbamoyl)adenosine, TC threon-2-N-ylcarbamoyl

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