1. The nature of arginine binding to lobster arginine kinase and the extent of its possible involvement with the ‘essential’ thiol group of the enzyme has been investigated with some inhibitory analogues of arginine. 2. Most of the analogues inhibit competitively, although mixed inhibition may occur if the α-carboxy group or α-amino group is absent. 3. The Ki values indicate that strength of binding depends on the length of the carbon chain (l-isoleucine>l-valine>l- α-aminobutyrate>l-alanine) and the integrity of the substituents on the α-carbon atom (l-arginine>agmatine and l-ornithine>putrescine). The guanidino group probably contributes little to substrate binding, but a positive charge near the δ-nitrogen atom appears to be important (l-ornithine>l -citrulline>l-α-aminobutyrate). A cyclic analogue, 2-carboxymethyl-3-oxo-2,3,5,6,7,8-hexahydro-1H-imidazo [1,2-a][1,3]diazepine-8-carboxylic acid, has a low Ki value similar to that of an equivalent straight-chain form, suggesting that arginine probably binds in a folded configuration. 4. The aliphatic l-amino acids give enzyme difference spectra similar to that with l-arginine and the integrity of the α-carboxy and α-amino groups appears to be a minimal but not sufficient requirement for this, as l-ornithine gives an atypical difference spectrum. A difference spectrum is interpreted as indicating an enzyme conformational change. No difference spectrum was observed with methylguanidine. 5. The ability of aliphatic α-l-amino acids to protect against inhibition by 5,5′-dithiobis-(2-nitrobenzoic acid) is proportional to the number of atoms in the carbon chain and inversely proportional to Ki. Ornithine gives greater protection than citrulline; analogues lacking the α-amino groups also protect. Agmatine, lacking the α-carboxy group, did not protect. 6. It is concluded that it is unlikely that the ‘essential’ thiol group in the enzyme interacts with any part of the arginine molecule during catalysis except, possibly, the α-carboxyl group.

This content is only available as a PDF.
You do not currently have access to this content.