PDBsum entry 3bpb

Hydrolase

PDB id: 3bpb

Contents

Protein chains

254 a.a. *

Ligands

SMZ ×2

Waters ×59

* Residue conservation analysis

PDB id:

3bpb

Name:

Hydrolase

Title:

Crystal structure of the dimethylarginine dimethylaminohydrolase h162g adduct with s-methyl-l-thiocitrulline

Structure:

Dimethylarginine dimethylaminohydrolase. Chain: a, b. Engineered: yes. Mutation: yes

Source:

Pseudomonas aeruginosa. Gene: pa1195. Expressed in: escherichia coli.

Resolution:

2.81Å R-factor: 0.233 R-free: 0.297

Authors:

A.F.Monzingo,T.W.Linsky,E.M.Stone,W.Fast,J.D.Robertus

Key ref:

T.W.Linsky et al. (2008). Promiscuous partitioning of a covalent intermediate common in the pentein superfamily. Chem Biol, 15, 467-475. PubMed id: 18482699

Date:

18-Dec-07 Release date: 17-Jun-08

Protein chains

Q9I4E3  (DDAH_PSEAE) -  N(G),N(G)-dimethylarginine dimethylaminohydrolase from Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1)

Seq: 254 a.a.

Struc: 254 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.5.3.18 - dimethylargininase.
• Reaction: N(omega),N(omega)-dimethyl-L-arginine + H2O = dimethylamine + L-citrulline

N(omega),N(omega)-dimethyl-L-arginine + H2O = dimethylamine + L-citrulline (Bound ligand (Het Group name = SMZ) matches with 91.67% similarity)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

Chem Biol 15:467-475 (2008)

PubMed id: 18482699

Promiscuous partitioning of a covalent intermediate common in the pentein superfamily.

T.W.Linsky, A.F.Monzingo, E.M.Stone, J.D.Robertus, W.Fast.

ABSTRACT

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.