Polymorphic Human arylamine N-acetyltransferase (NAT2) inactivates the anti-tubercular drug isoniazid by acetyltransfer from acetylCoA. There are active NAT proteins encoded by homologous genes in mycobacteria including M. tuberculosis, M. bovis BCG, M. smegmatis and M. marinum. Crystallographic structures of NATs from M. smegmatis and M. marinum, as native enzymes and with isoniazid bound share a similar fold with the first NAT structure, Salmonella typhimurium NAT. There are three approximately equal domains and an active site essential catalytic triad of cysteine, histidine and aspartate in the first two domains. An acetyl group from acetylCoA is transferred to cysteine and then to the acetyl acceptor e.g. isoniazid. M. marinum NAT binds CoA in a more open mode compared with CoA binding to human NAT2. The structure of mycobacterial NAT may promote its role in synthesis of cell wall lipids, identified through gene deletion studies. NAT protein is essential for survival of M. bovis BCG in macrophage as are the proteins encoded by other genes in the same gene cluster (hsaA-D). HsaA-D degrade cholesterol, essential for mycobacterial survival inside macrophage. Nat expression remains to be fully understood but is co-ordinated with hsaA-D and other stress response genes in mycobacteria.Amide synthase genes in the streptomyces are also nat homologues. The amide synthases are predicted to catalyse intramolecular amide bond formation and creation of cyclic molecules, e.g. geldanamycin. Lack of conservation of the CoA binding cleft residues of M. marinum NAT suggests the amide synthase reaction mechanism does not involve a soluble CoA intermediate during amide formation and ring closure.
‘Modernity’ has long been a working category of historical analysis in Russian and Soviet studies. Like any established category, it bears a history of its own characterised by founding assumptions, conceptual possibilities and lasting interpretive habits. Stephen Kotkin's work has played a special role in framing the kind of scholarship this category has enabled and the kind of modernity it has assigned to twentieth-century Russia. Kotkin's 1995 Magnetic Mountain introduced the concept of ‘socialist modernity’. His continued work with the concept in his 2001 Kritika article ‘Modern Times’ and his 2001 Armageddon Averted marked crucial moments in the history of the discipline and have positioned the author as a pioneering and dominant voice on the subject for nearly two decades. Given the defining nature of Kotkin's work, a critical discussion of its impact on the way the discipline conceives of Soviet modernisation and presents it to non-Russian fields is perhaps overdue. Here, I approach Kotkin's work on modernity as the field's collective property in need of a critical, deconstructive reading for its underlying assumptions, prescribed master narratives, and resultant paradoxes.
In contemporary gender history, the story about the making of the gender category is inseparable from the concept of ‘gender binary’. It at once signifies a research agenda and constitutes a persistent problem pervading feminist analysis itself. On the one hand, it points to the massive historical record of persistent inequality between the sexes. On the other hand, the concept of ‘gender binary’ undergirds gender history's analytics, which empowers historians to pursue, expose and deconstruct the binary organisation of gendered – woman/man – identities as well as social relations and discursive formations that produce them. In both capacities, the concept carries a rich repertoire of connotations, which informs and influences the gender category: those of radical distinction, opposition, mutually exclusive and exhaustive differentiation, hierarchy, domination, oppression – in all their myriad historical forms. As a result, it captures the entanglement of gender – in theory, an open‐ended category – in binary, that is, negatively and positively determined connotations of feminine and masculine and, consequently, in a particular, historical form of heterosexual subjectivity, the one structured like a binary system. The entanglement of gender history's foundational category – gender – in the binary systems of assigning difference has had many critics. What has been left unexamined however and what gives this article its focus is the poverty of gender as a binary device to analyse those gendered identities that constitute heterosexual relations but do not fit the binary matrix. The goal in this article is to enable the conditions for the continuous development – not abandonment – of the gender category and our theoretical framework. To do that, I explore how the gender category became a binary category, tightly identified with connotations of asymmetry and hierarchy, by undertaking a deconstructive rereading of a foundational work by one of the discipline's most influential poststructuralist theorists – Joan Scott. I conclude by arguing that in order to address the problem of gendered, heterosexual identities that do not fit the binary matrix we need to revisit the concept of dichotomy and differentiate it from binary connotations of difference found in heteronormative gender systems.
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