Steve Ealick's Research Group
Arginine Decarboxylase from Methanococcus jannaschii
1MT1 selenomethionyl arginine decarboxylase
1N13 pyruvoyl-dependent arginine decarboxylase complexed with agmatine
1N2M S53A proenzyme mutant of arginine decarboxylase
*2QQD, arginine decarboxylase N47A mutant
*2QQC, arginine decarboxylase E109Q mutant
Polyamines are essential factors required by all organisms. Two of the most common polyamines, spermine and spermidine, are biosynthesized from putrescine and the aminopropyl group of decarboxylated S-adenosylmethionine (AdoMet). Some cells produce putrescine directly by decarboxylating ornithine. The Methanococcus jannaschii archaeal enzyme uses a different pathway: L-arginine is decarboxylated to agmatine, which is converted to putrescine by agmatine ureohydrolase. The enzyme uses a pyruvoyl group, formed by protein self-cleavage as the cofactor. This enzyme is remarkably thermostable and retains 50% activity after heating for 30 min at 125 °C. The M. jannaschii genome encodes no recognizable PLP-dependent L-ornithine decarboxylase or PLP-dependent L-arginine decarboxylase.
|The monomer fold is a four-layer αββα sandwich. The pyruvoyl group and bound agamatine are shown in the diagram. The pyruvoyl group of arginine decarboxylase is generated by an autocatalytic internal serinolysis reaction at Ser53 in the proenzyme resulting in two polypeptide chains.|
|Arginine decarboxylase is a homotrimer. The pyruvoyl group is shown in each monomer as a ball-and-stick model.|
|Active sites of arginine decarboxylase are located at the interfaces of two protomers pointed inwards towards the threefold axis. Agmatine binding residues include the C-terminus of the b-chain (Ser52) from one protomer and the Asp35 side chain and the Gly44 and Val46 carbonyl oxygen atoms from an adjacent protomer.||
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Tolbert WD, Graham DE, White RH, and Ealick SE. Pyruvoyl-dependent Arginine Decarboxylase from Methanococcus jannaschii: Crystal Structures of the Self-cleaved and S53A Proenzyme Forms. Structure 11:285-294 (2003).
*Soriano EV, McCloskey DE, Kinsland C, Pegg AE and Ealick SE. Structures of the N47A and E109Q Mutant Proteins of Pyruvoyl-dependent Arginine Decarboxylase from Methanococcus jannaschii. Acta Crystallogr. D 64:377-382 (2008).