Summary for 1OHV
| Entry DOI | 10.2210/pdb1ohv/pdb |
| Related | 1OHW 1OHY |
| Descriptor | 4-AMINOBUTYRATE AMINOTRANSFERASE, ACETATE ION, PYRIDOXAL-5'-PHOSPHATE, ... (5 entities in total) |
| Functional Keywords | transferase, plp-dependent enzyme, aminotransferase, 4- aminobutyric acid, antiepileptic drug target |
| Biological source | SUS SCROFA (PIG) |
| Cellular location | Mitochondrion matrix: P80147 |
| Total number of polymer chains | 4 |
| Total formula weight | 215052.37 |
| Authors | Storici, P.,Schirmer, T. (deposition date: 2003-06-02, release date: 2003-10-16, Last modification date: 2023-12-13) |
| Primary citation | Storici, P.,De Biase, D.,Bossa, F.,Bruno, S.,Mozzarelli, A.,Peneff, C.,Silverman, R.,Schirmer, T. Structures of {Gamma}-Aminobutyric Acid (Gaba) Aminotransferase, a Pyridoxal 5'-Phosphate, and [2Fe-2S] Cluster-Containing Enzyme, Complexed with {Gamma}-Ethynyl-Gaba and with the Antiepilepsy Drug Vigabatrin J.Biol.Chem., 279:363-, 2004 Cited by PubMed Abstract: Gamma-aminobutyric acid aminotransferase (GABA-AT) is a pyridoxal 5'-phosphate-dependent enzyme responsible for the degradation of the inhibitory neurotransmitter GABA. GABA-AT is a validated target for antiepilepsy drugs because its selective inhibition raises GABA concentrations in brain. The antiepilepsy drug, gamma-vinyl-GABA (vigabatrin) has been investigated in the past by various biochemical methods and resulted in several proposals for its mechanisms of inactivation. In this study we solved and compared the crystal structures of pig liver GABA-AT in its native form (to 2.3-A resolution) and in complex with vigabatrin as well as with the close analogue gamma-ethynyl-GABA (to 2.3 and 2.8 A, respectively). Both inactivators form a covalent ternary adduct with the active site Lys-329 and the pyridoxal 5'-phosphate (PLP) cofactor. The crystal structures provide direct support for specific inactivation mechanisms proposed earlier on the basis of radio-labeling experiments. The reactivity of GABA-AT crystals with the two GABA analogues was also investigated by polarized absorption microspectrophotometry. The spectral data are discussed in relation to the proposed mechanism. Intriguingly, all three structures revealed a [2Fe-2S] cluster of yet unknown function at the center of the dimeric molecule in the vicinity of the PLP cofactors. PubMed: 14534310DOI: 10.1074/JBC.M305884200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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