Structural highlights
Function
[DAAA_BACYM] Acts on the D-isomers of alanine, leucine, aspartate, glutamate, aminobutyrate, norvaline and asparagine. The enzyme transfers an amino group from a substrate D-amino acid to the pyridoxal phosphate cofactor to form pyridoxamine and an alpha-keto acid in the first half-reaction. The second-half reaction is the reverse of the first, transferring the amino group from the pyridoxamine to a second alpha-keto acid to form the product D-amino acid via a ping-pong mechanism. This is an important process in the formation of D-alanine and D-glutamate, which are essential bacterial cell wall components.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Mechanism-based inhibitors such as cycloserine and gabaculine can inactivate aminotransferases via reactions of the compounds with the pyridoxal phosphate cofactor forming an irreversible adduct. The reaction is chirally specific in that any one enzyme usually only recognizes one enantiomer of the inactivator. For instance, L-aspartate aminotransferase (L-AspAT) is inactivated by 4-amino-4,5-dihydro-2-thiophenecarboxylic acid (ADTA); however, only by the S-isomer. We have now shown that D-amino acid aminotransferase (D-a-AT) is irreversibly inactivated by the R-isomer of the same compound. The X-ray crystal structure (PDB Code: 3LQS) of the inactivated enzyme shows that in the product the enzyme no longer makes a Schi ff base linkage to the pyridoxal-5'-phosphate (PLP) cofactor, and instead the compound has formed a derivative of the cofactor. The adduct is similar to that formed between D-cycloserine and D-a-AT or alanine racemase (Ala-Rac) in that the thiophene ring of R-ADTA is intact and seems to be aromatic. The plane of the ring is rotated by nearly 90 degrees with respect to the plane of the pyridine ring of the cofactor, in comparison with the enzyme inactivated by cycloserine. Based on the structure of the product, the mechanism of inactivation most probably involves a transamination followed by aromatization to form an aromatic thiophene ring.
Chiral discrimination among aminotransferases: inactivation by 4-amino-4,5-dihydro-thiophenecarboxylic acid (ADTA).,Lepore BW, Liu D, Peng Y, Fu M, Yasuda C, Manning JM, Silverman RB, Ringe D Biochemistry. 2010 Mar 1. PMID:20192272[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tanizawa K, Masu Y, Asano S, Tanaka H, Soda K. Thermostable D-amino acid aminotransferase from a thermophilic Bacillus species. Purification, characterization, and active site sequence determination. J Biol Chem. 1989 Feb 15;264(5):2445-9. PMID:2914916
- ↑ Peisach D, Chipman DM, Van Ophem PW, Manning JM, Ringe D. Crystallographic study of steps along the reaction pathway of D-amino acid aminotransferase. Biochemistry. 1998 Apr 7;37(14):4958-67. PMID:9538014 doi:10.1021/bi972884d
- ↑ Lepore BW, Liu D, Peng Y, Fu M, Yasuda C, Manning JM, Silverman RB, Ringe D. Chiral discrimination among aminotransferases: inactivation by 4-amino-4,5-dihydro-thiophenecarboxylic acid (ADTA). Biochemistry. 2010 Mar 1. PMID:20192272 doi:10.1021/bi902052x
