Plasticity, ligand conformation and enzyme action of Mycobacterium smegmatis MutT1

Abstract

Mycobacterium smegmatis MutT1 (MsMutT1) is a sanitation enzyme made up of an N-terminal Nudix hydrolase domain and a C-terminal domain resembling a histidine phosphatase. It has been established that the action of MutT1 on 8-oxo-dGTP, 8-oxo-GTP and diadenosine polyphosphates is modulated by intermolecular interactions. In order to further explore this and to elucidate the structural basis of its differential action on 8-oxo-NTPs and unsubstituted NTPs, the crystal structures of complexes of MsMutT1 with 8-oxo-dGTP, GMPPNP and GMPPCP have been determined. Replacement soaking was used in order to ensure that the complexes were isomorphous to one another. Analysis of the structural data led to the elucidation of a relationship between the arrangements of molecules observed in the crystals, molecular plasticity and the action of the enzyme on nucleotides. The dominant mode of arrangement involving a head-to-tail sequence predominantly leads to the generation of NDPs. The other mode of packing arrangement appears to preferentially generate NMPs. This work also provides interesting insights into the dependence of enzyme action on the conformation of the ligand. The possibility of modulating the enzyme action through differences in intermolecular interactions and ligand conformations makes MsMutT1 a versatile enzyme.

Effect of Cognitive Control on Attentional Processing of Emotional Information Among Older Adults: Evidence From an Eye-Tracking Study

“…However, others using pupil size as an indicator of cognitive effort have found that older adults make little effort to engage in a positive gaze when experiencing a negative mood ( Allard et al, 2010 ). Their findings are seemingly confounded by the argument that PE is involved in top-down, voluntary cognitive control processes ( Henderickx et al, 2009 ; Reed and Carstensen, 2012 ; Sakaki et al, 2019 ). One possible reason for these mixed findings is that age-by-valence PE is not only dependent on different task demands accounting for the cognitive load ( Lavie, 2005 ; Mark and Murray, 2017 ) but also affected by different attentional engagement and disengagement processes ( Demeyer et al, 2017 ).…”

The Cardiovascular Conundrum in Ethnic and Sexual Minorities: A Potential Biomarker of Constant Coping With Discrimination

“…Sexual minorities appear to be the optimal population to study with this regard, as they are characterized by increased risk of stigma and prejudice ( Herek, 2004 ). Through the minority stress model , Meyer (2003) conceptualized stigma as a source of psychosocial stress that is additive to the other stressors that are experienced by the majority of people and chronic because it depends on quite stable social and cultural structures.…”

Dialogic Feminist Gathering and the Prevention of Gender Violence in Girls With Intellectual Disabilities

“…The case study has followed the principles of the communicative methodology that “emphasizes that egalitarian dialogues between researchers and the life world of the subjects under investigation are necessary to achieve higher levels of Social Justice” ( Gómez-González et al, 2010 ). In the dialog with the research participants, the researchers present data and arguments about the issues based on the scientific production on the subject.…”

“…The communicative techniques used for the collection of empirical materials and the communicative analysis for this research were: two in-depth interviews, one with the director of the special school and another with the DFG coordinator; a focus group only with the female teachers participating in the DFG, and a field diary in which the coordinator of the DFGs recorded the interventions of the girls with intellectual disabilities participating in the meetings, the topics and the selected scientific content. The focus group in a communicative approach ( Gómez-González et al, 2010 ) is organized from the natural group of people who already know each other; in the case studied, they were teachers who regularly participated in the DFGs and who freely agreed to participate in the research. As for the field diary notes, when necessary, the researchers asked the DFG coordinator for clarifications about the procedures, meetings, materials, and transcription of the speeches of the girls with special needs participating in the meetings.…”

“…The analysis of the information gathered from the transcripts of the two interviews, the focus group and the accounts recorded in the field diary, has been based on the two components of the communicative methodology: (1) the exclusionary dimension, which identifies the barriers that prevent transformation, since in the absence of these barriers, practices or social benefits would be available to excluded individuals or groups ( Gómez-González et al, 2010 ) and (2) the transformative dimension, which includes the elements that overcome such barriers. Importantly, research on sexual violence prevention done with the communicative methodology shows that it is distinguished by its contributions to advancing the identification, prevention, and overcoming of gender-based violence ( Puigvert, 2014 ), which can help health care providers and others caring for young women identify whether they have been victims of gender-based violence ( Ruiz-Eugenio et al, 2020 ).…”