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Substrate inhibition of D-amino acid transaminase and protection by salts and by reduced nicotinamide adenine dinucleotide: isolation and initial characterization of a pyridoxo intermediate related to inactivation.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Ophem, P. W. Van Erickson, Shawn D. Pozo, A. Martínez Del Haller, Irene M. Chait, Brian T. Yoshimura, Tohru Soda, Kenji Ringe, Dagmar Petsko, Gregory A. Manning, James M. |
| Copyright Year | 1998 |
| Abstract | D-Amino acid transaminase, a pyridoxal phosphate (PLP) enzyme, is inactivated by its natural substrate, D-alanine, concomitant with its alpha-decarboxylation [Martinez del Pozo, A., Yoshimura, T., Bhatia, M. B., Futaki, S., Manning, J. M., Ringe, D., and Soda, K. (1992) Biochemistry 31, 6018-6023; Bhatia, M. B., Martinez del Pozo, A., Ringe, D., Yoshimura, T., Soda, K., and Manning, J. M. (1993) J. Biol. Chem. 268, 17687-17694]. beta-Decarboxylation of d-aspartate to d-alanine leads also to this inactivation [Jones, W. M., van Ophem, P. W., Pospischil, M. A., Ringe, D., Petsko, G., Soda, K., and Manning, J. M. (1996) Protein Sci. 5, 2545-2551]. Using a high-performance liquid chromatography-based method for the determination of pyridoxo cofactors, we detected a new intermediate closely related to the inactivation by d-alanine; its formation occurred at the same rate as the inactivation and upon reactivation it reverted to PLP. Conditions were found under which it was characterized by ultraviolet-visible spectral analysis and mass spectroscopy; it is a pyridoxamine phosphate-like compound with a C2 fragment derived from the substrate attached to the C'-4 of the pyridinium ring and it has a molecular mass of 306 consistent with this structure. In the presence of d-serine, slow accumulation of a quinonoid intermediate is also related to inactivation. The inactivation can be prevented by salts, which possibly stabilize the protonated aldimine coenzyme complex. The reduced cofactor, nicotinamide adenine dinucleotide, prevents D-aspartate-induced inactivation. Both of these events also are related to formation of the novel intermediate. |
| Starting Page | 77 |
| Ending Page | 80 |
| Page Count | 4 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://lab.rockefeller.edu/chait/pdf/98/98_ophem_biochem.pdf |
| PubMed reference number | 9485439v1 |
| Volume Number | 37 |
| Issue Number | 9 |
| Journal | Biochemistry |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 3-hydroxy-3-methylglutaryl-coenzyme A Alanine Transaminase Amino Acids Aspartate Transaminase Aspartic Acid Chromosome Deletion Coenzymes Decarboxylation Dinucleoside Phosphates Flavin-Adenine Dinucleotide Liquid Chromatography Mass Spectrometry Molecular Mass Niacin Niacinamide Nicotinamide adenine dinucleotide (NAD) Pyridoxal Phosphate Reactivation Salts Thioctic Acid Transaminases chemical cofactor inorganic phosphate pyridoxamine phosphate serine, D- type I interferon receptor |
| Content Type | Text |
| Resource Type | Article |
