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Active site architecture of alanine aminotransferases.

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posted on 11.07.2014, 02:53 by Esther Peña-Soler, Francisco J. Fernandez, Miguel López-Estepa, Fernando Garces, Andrew J. Richardson, Juan F. Quintana, Kenneth E. Rudd, Miquel Coll, M. Cristina Vega

Catalytically important amino acids and the cofactor of alanine transaminases: AlaA (A), PfAlaAT (PDB 1xi9) (B), human ALT2 (PDB 3ihj) (C) and HvAlaAT (PDB 3tcm) (D) are represented in sticks and color coded as in Figure 3. Dashed lines represent polar interactions. (A) Carbon atoms of the acetate anion are shown in green. (B) PfAlaAT in the PMP form with a disordered N-terminal segment. The pyridoxamine ring of PMP is packed between Ile207 and Tyr127 (not shown for clarity). (C) In ALT2 all active-site residues pinpointed in AlaA (A) and PfAlaAT (B) are structurally conserved, except for the residue equivalent to Gly41 (AlaA)/Gly38 (PfAlaAT). Gly96 (ALT2), which falls in a disordered loop (Ile95 to Gln104), is a likely candidate to assume the substrate-binding role of Gly41 (AlaA) because of its proximity. (D) The suicide inhibitor complex of D-cycloserine (DCS) in the active site of HvAlaAT assumes an identical configuration to that of AlaA, likewise accompanied by a fully ordered N-terminal motif that is closer in structure to the bacterial/archeal enzymes than to the human ALT2 despite the 44% sequence identity (by comparison, HvAlaAT and AlaA are only 28% sequence identical).

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