Limits...
Long-lasting effects of oxy- and sulfoanalogues of L-arginine on enzyme actions.

Dzimbova TA, Milanov PB, Pajpanova TI - J Amino Acids (2013)

Bottom Line: We make use of modeling and docking studies of adenylate kinase (ADK) to reveal the effects produced by the incorporation of the arginine mimetics on the structure of ADK and its action.Mutation in the enzyme active center by arginine mimetics leads to conformational changes, which produce a decrease the rate of the enzyme catalyzed reaction and even a loss of enzymatic action.All these observations could explain the long-lasting nature of the effects of the arginine analogues.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Biology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.

ABSTRACT
Arginine residues are very important for the structure of proteins and their action. Arginine is essential for many natural processes because it has unique ionizable group under physiological conditions. Numerous mimetics of arginine were synthesized and their biological effects were evaluated, but the mechanisms of actions are still unknown. The aim of this study is to see if oxy- and sulfoanalogues of arginine can be recognized by human arginyl-tRNA synthetase (HArgS)-an enzyme responsible for coupling of L-arginine with its cognate tRNA in a two-step catalytic reaction. We make use of modeling and docking studies of adenylate kinase (ADK) to reveal the effects produced by the incorporation of the arginine mimetics on the structure of ADK and its action. Three analogues of arginine, L-canavanine (Cav), L-norcanavanine (NCav), and L-sulfoarginine (sArg), can be recognized as substrates of HArgS when incorporated in different peptide and protein sequences instead of L-arginine. Mutation in the enzyme active center by arginine mimetics leads to conformational changes, which produce a decrease the rate of the enzyme catalyzed reaction and even a loss of enzymatic action. All these observations could explain the long-lasting nature of the effects of the arginine analogues.

No MeSH data available.


Related in: MedlinePlus

Superposition of the sequence GAGKG (25–29): (a) ADK and ADK mutated with Cav138 (blue), NCav138 (green), and sArg138 (purple); (b) ADK and ADK mutated with Cav175 (blue), NCav175 (green), and sArg175 (purple).
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3824642&req=5

fig8: Superposition of the sequence GAGKG (25–29): (a) ADK and ADK mutated with Cav138 (blue), NCav138 (green), and sArg138 (purple); (b) ADK and ADK mutated with Cav175 (blue), NCav175 (green), and sArg175 (purple).

Mentions: Exploring the sequence GAGKG in the case of Arg138 mutation, the biggest conformational changes occurred when Arg138 is replaced by NCav (Figure 8(a)).


Long-lasting effects of oxy- and sulfoanalogues of L-arginine on enzyme actions.

Dzimbova TA, Milanov PB, Pajpanova TI - J Amino Acids (2013)

Superposition of the sequence GAGKG (25–29): (a) ADK and ADK mutated with Cav138 (blue), NCav138 (green), and sArg138 (purple); (b) ADK and ADK mutated with Cav175 (blue), NCav175 (green), and sArg175 (purple).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3824642&req=5

fig8: Superposition of the sequence GAGKG (25–29): (a) ADK and ADK mutated with Cav138 (blue), NCav138 (green), and sArg138 (purple); (b) ADK and ADK mutated with Cav175 (blue), NCav175 (green), and sArg175 (purple).
Mentions: Exploring the sequence GAGKG in the case of Arg138 mutation, the biggest conformational changes occurred when Arg138 is replaced by NCav (Figure 8(a)).

Bottom Line: We make use of modeling and docking studies of adenylate kinase (ADK) to reveal the effects produced by the incorporation of the arginine mimetics on the structure of ADK and its action.Mutation in the enzyme active center by arginine mimetics leads to conformational changes, which produce a decrease the rate of the enzyme catalyzed reaction and even a loss of enzymatic action.All these observations could explain the long-lasting nature of the effects of the arginine analogues.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Biology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria.

ABSTRACT
Arginine residues are very important for the structure of proteins and their action. Arginine is essential for many natural processes because it has unique ionizable group under physiological conditions. Numerous mimetics of arginine were synthesized and their biological effects were evaluated, but the mechanisms of actions are still unknown. The aim of this study is to see if oxy- and sulfoanalogues of arginine can be recognized by human arginyl-tRNA synthetase (HArgS)-an enzyme responsible for coupling of L-arginine with its cognate tRNA in a two-step catalytic reaction. We make use of modeling and docking studies of adenylate kinase (ADK) to reveal the effects produced by the incorporation of the arginine mimetics on the structure of ADK and its action. Three analogues of arginine, L-canavanine (Cav), L-norcanavanine (NCav), and L-sulfoarginine (sArg), can be recognized as substrates of HArgS when incorporated in different peptide and protein sequences instead of L-arginine. Mutation in the enzyme active center by arginine mimetics leads to conformational changes, which produce a decrease the rate of the enzyme catalyzed reaction and even a loss of enzymatic action. All these observations could explain the long-lasting nature of the effects of the arginine analogues.

No MeSH data available.


Related in: MedlinePlus