Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

2-Amino-3-ketobutyrate CoA ligase (KBL, EC 2.3.1.29) is a pyridoxal phosphate (PLP) dependent enzyme, which catalyzes the second reaction step on the main metabolic degradation pathway for threonine. It acts in concert with threonine dehydrogenase and converts 2-amino-3-ketobutyrate, the product of threonine dehydrogenation by the latter enzyme, with the participation of cofactor CoA, to glycine and acetyl-CoA. The enzyme has been well conserved during evolution, with 54% amino acid sequence identity between the Escherichia coli and human enzymes. We present the three-dimensional structure of E. coli KBL determined at 2.0 A resolution. KBL belongs to the alpha family of PLP-dependent enzymes, for which the prototypic member is aspartate aminotransferase. Its closest structural homologue is E. coli 8-amino-7-oxononanoate synthase. Like many other members of the alpha family, the functional form of KBL is a dimer, and one such dimer is found in the asymmetric unit in the crystal. There are two active sites per dimer, located at the dimer interface. Both monomers contribute side chains to each active/substrate binding site. Electron density maps indicated the presence in the crystal of the Schiff base intermediate of 2-amino-3-ketobutyrate and PLP, an external aldimine, which remained bound to KBL throughout the protein purification procedure. The observed interactions between the aldimine and the side chains in the substrate binding site explain the specificity for the substrate and provide the basis for a detailed proposal of the reaction mechanism of KBL. A putative binding site of the CoA cofactor was assigned, and implications for the cooperation with threonine dehydrogenase were considered.
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PMID:Three-dimensional structure of 2-amino-3-ketobutyrate CoA ligase from Escherichia coli complexed with a PLP-substrate intermediate: inferred reaction mechanism. 1131 37

New Council of Europe regulations mandate housing of two rabbits in the same cage space currently used to house one, provided the animals are socially compatible. This study was designed to assess changes in growth and selected serum chemistry parameters due to pair housing or single housing of rabbits. Six sets of four female siblings of Crl:KBL(NZW)BR rabbits were used. The animals were seven weeks old on arrival. Two siblings of each set were allocated to pair housing, two to single housing. The animals were housed in stainless steel cages (120 cm x 60 cm x 60 cm) with a perforated floor, including a shelf (60 cm x 30 cm) at 30 cm height from the floor. The rabbits were provided with an aspen cube (5 cm x 5 cm x 5 cm), one item per animal. The rabbits were weighed and blood samples were taken from the auricular central artery at four different times during the study. Blood sera were assayed for a set of routinely assayed clinical chemistry parameters: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (APHOS), blood urea nitrogen (BUN), cholesterol (CHOL) and protein (PROT). Mean and variance profiles over the study period were statistically analysed by multivariate analysis of variance. No differences in mean profiles were detected; however, weight (P = 0.0002) and APHOS (P = 0.017) variances were significantly lower in pair-housed animals. The reduction in variance on growth and APHOS attributable to pair housing appears to be rather large. During the 21-week study, occasional fighting was seen between the pair-housed rabbits. After sexual maturity, further major fighting bouts resulted in significant trauma that necessitated the cessation of the study. In conclusion, pair housing appears to have a decreasing effect on growth and APHOS variance, but antisocial behaviour such as fighting remains a serious problem.
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PMID:Pair housing of rabbits reduces variances in growth rates and serum alkaline phosphatase levels. 1798 38