3BPB: Crystal Structure Of The Dimethylarginine Dimethylaminohydrolase H162g Adduct With S-methyl-l-thiocitrulline

Many 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.
PDB ID: 3BPBDownload
MMDB ID: 64976
PDB Deposition Date: 2007/12/18
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.81  Å
Source Organism:
Similar Structures:
Biological Unit for 3BPB: monomeric; determined by software (PISA)
Molecular Components in 3BPB
Label Count Molecule
Protein (1 molecule)
Dimethylarginine Dimethylaminohydrolase(Gene symbol: PA1195)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB