3bpb
Crystal structure of the dimethylarginine dimethylaminohydrolase H162G adduct with S-methyl-L-thiocitrullineCrystal structure of the dimethylarginine dimethylaminohydrolase H162G adduct with S-methyl-L-thiocitrulline
Structural highlights
FunctionDDAH_PSEAE Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedMany enzymes in the pentein superfamily use a transient covalent intermediate in their catalytic mechanisms. Here we trap and determine the structure of a stable covalent adduct that mimics this intermediate using a mutant dimethylarginine dimethylaminohydrolase and an alternative substrate. The interactions observed between the enzyme and trapped adduct suggest an altered angle of attack between the nucleophiles of the first and second half-reactions of normal catalysis. The stable covalent adduct is also capable of further reaction. Addition of imidazole rescues the original hydrolytic activity. Notably, addition of other amines instead yields substituted arginine products, which arise from partitioning of the intermediate into the evolutionarily related amidinotransferase reaction pathway. The enzyme provides both selectivity and catalysis for the amidinotransferase reaction, underscoring commonalities among the reaction pathways in this mechanistically diverse enzyme superfamily. The promiscuous partitioning of this intermediate may also help to illuminate the evolutionary history of these enzymes. Promiscuous partitioning of a covalent intermediate common in the pentein superfamily.,Linsky TW, Monzingo AF, Stone EM, Robertus JD, Fast W Chem Biol. 2008 May;15(5):467-75. PMID:18482699[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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