2JBW
Crystal Structure of the 2,6-dihydroxy-pseudo-oxynicotine Hydrolase.
Summary for 2JBW
| Entry DOI | 10.2210/pdb2jbw/pdb |
| Descriptor | 2,6-DIHYDROXY-PSEUDO-OXYNICOTINE HYDROLASE, SODIUM ION (3 entities in total) |
| Functional Keywords | hydrolase, alpha/beta hydrolase, meta-cleavage pathway, retro- friedel- crafts acylation, nicotine degradation, hypothetical protein, plasmid, catalytic triad, c-c bond cleavage |
| Biological source | ARTHROBACTER NICOTINOVORANS |
| Total number of polymer chains | 4 |
| Total formula weight | 175537.88 |
| Authors | Schleberger, C.,Sachelaru, P.,Brandsch, R.,Schulz, G.E. (deposition date: 2006-12-14, release date: 2007-01-04, Last modification date: 2024-11-06) |
| Primary citation | Schleberger, C.,Sachelaru, P.,Brandsch, R.,Schulz, G.E. Structure and Action of a Cc Bond Cleaving Alpha/Beta-Hydrolase Involved in Nicotine Degration. J.Mol.Biol., 367:409-, 2007 Cited by PubMed Abstract: The enzyme 2,6-dihydroxy-pseudo-oxynicotine hydrolase from the nicotine-degradation pathway of Arthrobacter nicotinovorans was crystallized and the structure was determined by an X-ray diffraction analysis at 2.1 A resolution. The enzyme belongs to the alpha/beta-hydrolase family as derived from the chain-fold and from the presence of a catalytic triad with its oxyanion hole at the common position. This relationship assigns a pocket lined by the catalytic triad as the active center. The asymmetric unit contains two C(2)-symmetric dimer molecules, each adopting a specific conformation. One dimer forms a more spacious active center pocket and the other a smaller one, suggesting an induced-fit. All of the currently established C-C bond cleaving alpha/beta-hydrolases are from bacterial meta-cleavage pathways for the degradation of aromatic compounds and cover their active center with a 40 residue lid placed between two adjacent strands of the beta-sheet. In contrast, the reported enzyme shields its active center with a 110 residue N-terminal domain, which is absent in the meta-cleavage hydrolases. Since neither the substrate nor an analogue could be bound in the crystals, the substrate was modeled into the active center using the oxyanion hole as a geometric constraint. The model was supported by enzymatic activity data of 11 point mutants and by the two dimer conformations suggesting an induced-fit. Moreover, the model assigned a major role for the large N-terminal domain that is specific to the reported enzyme. The proposal is consistent with the known data for the meta-cleavage hydrolases although it differs in that the reaction does not release alkenes but a hetero-aromatic compound in a retro-Friedel-Crafts acylation. Because the hydrolytic water molecule can be assigned to a geometrically suitable site that can be occupied in the presence of the substrate, the catalytic triad may not form a covalent acyl-enzyme intermediate but merely support a direct hydrolysis. PubMed: 17275835DOI: 10.1016/J.JMB.2006.12.068 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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