Amino Acid Chirality: Stereospecific Conversion and Physiological Implications.

The absolute configuration dictates the biological role of chiral molecules in the living world. This is best exemplified by all ribosomally synthesized polypeptides having chiral amino acids only in the l-configuration. However, d-amino acids are also associated with various vital biological processes such as peptidoglycan of the bacterial cell wall, ligands for neurotransmitters, molecules involved in signaling, and precursors of metabolites, to name a few. The occurrence of both l- and d-enantiomers of amino acids in the living systems necessitates the presence of enzymes that exhibit stereoselectivity in recognition of substrates. This mini-review summarizes the overall mechanistic insights into the interconversion of l- and d-amino acids by the amino acid racemases. We discuss the structural, mechanistic, and evolutionary relationship of four crucial enzymes that catalyze the oxidative deamination of l- or d-amino acids and their physiological role in microbes and higher organisms. We highlight the physiological implications of d-amino acid oxidase and d-aspartate oxidase in human health and diseases and their applications as drug targets. Finally, we summarize the potential applications of microbially obtained chiral-selective enzymes as biocatalysts and for various industrial purposes.

Functional plasticity in chromosome-microtubule coupling on the evolutionary time scale.

The Dam1 complex is essential for mitotic progression across evolutionarily divergent fungi. Upon analyzing amino acid (aa) sequences of Dad2, a Dam1 complex subunit, we identified a conserved 10-aa-long Dad2 signature sequence (DSS). An arginine residue (R126) in the DSS is essential for viability in Saccharomyces cerevisiae that possesses point centromeres. The corresponding arginine residues are functionally important but not essential for viability in Candida albicans and Cryptococcus neoformans; both carry several kilobases long regional centromeres. The purified recombinant Dam1 complex containing either Dad2ΔDSS or Dad2R126A failed to bind microtubules (MTs) or form any visible rings like the WT complex. Intriguingly, functional analysis revealed that the requirement of the conserved arginine residue for chromosome biorientation and mitotic progression reduced with increasing centromere length. We propose that plasticity of the invariant arginine of Dad2 in organisms with regional centromeres is achieved by conditional elevation of the kinetochore protein(s) to enable multiple kinetochore MTs to bind to each chromosome. The capacity of a chromosome to bind multiple kinetochore MTs may mask the deleterious effects of such lethal mutations.