Mass balance and metabolism of Z-215, a novel proton pump inhibitor, in healthy volunteers.

The human mass balance of [C]Z-215, a novel proton pump inhibitor, was characterised in six healthy male volunteers following single oral administration of [C]Z-215 (20 mg, 3.7 MBq) to determine the elimination pathway of Z-215 and the distribution of its metabolites in plasma, urine, and faeces (NCT02618629). [C]Z-215 was rapidly absorbed, with a C of 434 ng/mL at 0.

Dual roles of a conserved pair, Arg23 and Ser20, in recognition of multiple substrates in alpha-aminoadipate aminotransferase from Thermus thermophilus.

To clarify the mechanism for substrate recognition of alpha-aminoadipate aminotransferase (AAA-AT) from Thermus thermophilus, the crystal structure of AAA-AT complexed with N-(5'-phosphopyridoxyl)-l-glutamate (PPE) was determined at 1.67 A resolution. The crystal structure revealed that PPE is recognized by amino acid residues the same as those seen in N-(5'-phosphopyridoxyl)-l-alpha-aminoadipate (PPA) recognition; however, to bind the gamma-carboxyl group of Glu at a fixed position, the Calpha atom of the Glu moiety moves 0.

Mechanism for multiple-substrates recognition of alpha-aminoadipate aminotransferase from Thermus thermophilus.

Alpha-aminoadipate aminotransferase (AAA-AT), a homolog of mammalian kynurenine aminotransferase II (Kat II), transfers an amino group to 2-oxoadipate to yield alpha-aminoadipate in lysine biosynthesis through the alpha-aminoadipate pathway in Thermus thermophilus. AAA-AT catalyzes transamination against various substrates, including AAA, glutamate, leucine, and aromatic amino acids. To elucidate the structural change for recognition of various substrates, we determined crystal structures of AAA-AT in four forms: with pyridoxal 5'-phosphate (PLP) (PLP complex), with PLP and leucine (PLP/Leu complex), with N-phosphopyridoxyl-leucine (PPL) (PPL complex), and with N-phosphopyridoxyl-alpha-aminoadipate (PPA) at 2.