3paa | pdb_00003paa

Mechanism of inactivation of E. coli aspartate aminotransferase by (S)-4-amino-4,5-dihydro-2-furancarboxylic acid (S-ADFA) pH 8.0

spinqualitylabelsall models 3paa, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3paa is a 1 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: GOL, PJ7, PMP, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function D3H0F7_ECO44 Publication Abstract from PubMed As a potential drug to treat neurological diseases, the mechanism-based inhibitor (S)-4-amino-4,5-dihydro-2-furancarboxylic acid (S-ADFA) has been found to inhibit the gamma-aminobutyric acid aminotransferase (GABA-AT) reaction. To circumvent the difficulties in structural studies of a S-ADFA-enzyme complex using GABA-AT, l-aspartate aminotransferase (l-AspAT) from Escherichia coli was used as a model PLP-dependent enzyme. Crystal structures of the E. coli aspartate aminotransferase with S-ADFA bound to the active site were obtained via cocrystallization at pH 7.5 and 8. The complex structures suggest that S-ADFA inhibits the transamination reaction by forming adducts with the catalytic lysine 246 via a covalent bond while producing 1 equiv of pyridoxamine 5'-phosphate (PMP). Based on the structures, formation of the K246-S-ADFA adducts requires a specific initial binding configuration of S-ADFA in the l-AspAT active site, as well as deprotonation of the epsilon-amino group of lysine 246 after the formation of the quinonoid and/or ketimine intermediate in the overall inactivation reaction. Mechanism of Inactivation of Escherichia coli Aspartate Aminotransferase by (S)-4-Amino-4,5-dihydro-2-furancarboxylic Acid .,Liu D, Pozharski E, Fu M, Silverman RB, Ringe D Biochemistry. 2010 Nov 15. PMID:21033689 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aspartate aminotransferase 3D structures

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