2OIZ
Crystal Structure of the Tryptamine-Derived (Indol-3-Acetamide)-TTQ Adduct of Aromatic Amine Dehydrogenase
Summary for 2OIZ
| Entry DOI | 10.2210/pdb2oiz/pdb |
| Descriptor | Aromatic amine dehydrogenase, small subunit, Aromatic amine dehydrogenase, large subunit, 2-(1H-INDOL-3-YL)ACETAMIDE, ... (5 entities in total) |
| Functional Keywords | oxidoreductase, tryptophan tryptophyl quinone, h-tunneling |
| Biological source | Alcaligenes faecalis More |
| Total number of polymer chains | 4 |
| Total formula weight | 109608.67 |
| Authors | Roujeinikova, A.,Leys, D. (deposition date: 2007-01-12, release date: 2007-04-24, Last modification date: 2023-12-27) |
| Primary citation | Roujeinikova, A.,Hothi, P.,Masgrau, L.,Sutcliffe, M.J.,Scrutton, N.S.,Leys, D. New insights into the reductive half-reaction mechanism of aromatic amine dehydrogenase revealed by reaction with carbinolamine substrates. J.Biol.Chem., 282:23766-23777, 2007 Cited by PubMed Abstract: Aromatic amine dehydrogenase uses a tryptophan tryptophylquinone (TTQ) cofactor to oxidatively deaminate primary aromatic amines. In the reductive half-reaction, a proton is transferred from the substrate C1 to betaAsp-128 O-2, in a reaction that proceeds by H-tunneling. Using solution studies, kinetic crystallography, and computational simulation we show that the mechanism of oxidation of aromatic carbinolamines is similar to amine oxidation, but that carbinolamine oxidation occurs at a substantially reduced rate. This has enabled us to determine for the first time the structure of the intermediate prior to the H-transfer/reduction step. The proton-betaAsp-128 O-2 distance is approximately 3.7A, in contrast to the distance of approximately 2.7A predicted for the intermediate formed with the corresponding primary amine substrate. This difference of approximately 1.0 A is due to an unexpected conformation of the substrate moiety, which is supported by molecular dynamic simulations and reflected in the approximately 10(7)-fold slower TTQ reduction rate with phenylaminoethanol compared with that with primary amines. A water molecule is observed near TTQ C-6 and is likely derived from the collapse of the preceding carbinolamine TTQ-adduct. We suggest this water molecule is involved in consecutive proton transfers following TTQ reduction, and is ultimately repositioned near the TTQ O-7 concomitant with protein rearrangement. For all carbinolamines tested, highly stable amide-TTQ adducts are formed following proton abstraction and TTQ reduction. Slow hydrolysis of the amide occurs after, rather than prior to, TTQ oxidation and leads ultimately to a carboxylic acid product. PubMed: 17475620DOI: 10.1074/jbc.M700677200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.05 Å) |
Structure validation
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