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The enzyme malonamidase E2 catalytically hydrolyzes malonamate (MLA) into malonate and ammonia. Its active site contains an uncommon Ser-cisSer-Lys catalytic triad that is critical to its functioning. Mutations of the residues in this triad can not only provide insight into its key features but also potentially identify how it may be influenced or adapted, i.e., decreased or increased. In this study, the effects of single and double Ser/Cys exchanges on the wild-type Ser155-cisSer131-Lys62 catalytic triad (i.e., Cys155--cisSer131-Lys62 (S155C), Ser155--cisCys131--Lys62 (S131C), and Cys155--cisCys131--Lys62 (S131C/S155C) were examined. In particular, the dynamics and stability of the resulting substituted triads were examined along with their intertriad residue hydrogen bonding interactions as well as those with other nearby residues and the MLA substrate. The present results suggest that some mutations are more impactful than others. Indeed, mutation of cisSer131 to cisCysl31 disrupts the triad and causes inconsistent hydrogen bonding interactions among the triad residues (i.e., Ser155, Cys131, and Lys62). In contrast, in the double mutant Cys155-cisCys131-Lys62, the triad's residues appear to exhibit greater conformation stability with more consistent hydrogen bond interactions, though not necessarily as in the wild type. Key words: point mutation, Ser/Cys exchange, catalytic triad, molecular dynamics simulations, Introduction A key contributor to an enzyme's catalytic ability is the structure and composition of its active site(s). (1) The importance of coordinated spatial arrangement of residues, and their functionalities, [...]

Tuberculosis (TB) researchers and clinicians, by virtue of the social disease they study, are drawn into an engagement with ways of understanding illness that extend beyond the strictly biomedical model. Primers on social science concepts directly relevant to TB, however, are lacking. The particularities of TB disease mean that certain social science concepts are more relevant than others. Concepts such as structural violence can seem complicated and off-putting. Other concepts, such as gender, can seem so familiar that they are left relatively unexplored. An intimate familiarity with the social dimensions of disease is valuable, particularly for infectious diseases, because the social model is an important complement to the biomedical model. This review article offers an important introduction to a selection of concepts directly relevant to TB from health sociology, medical anthropology and social cognitive theory. The article has pedagogical utility and also serves as a useful refresher for those researchers already engaged in this genre of work. The conceptual tools of health sociology, medical anthropology and social cognitive theory offer insightful ways to examine the social, historical and cultural dimensions of public health. By recognizing cultural experience as a central force shaping human interactions with the world, TB researchers and clinicians develop a more nuanced consideration of how health, illness and medical treatment are understood, interpreted and confronted. [ABSTRACT FROM AUTHOR]