Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2

Search results for: Mark-Adam Kellerman

2 Mapping Structurally Significant Areas of G-CSF during Thermal Degradation with NMR

Authors: Mark-Adam Kellerman


Proteins are capable of exploring vast mutational spaces. This makes it difficult for protein engineers to devise rational methods to improve stability and function via mutagenesis. Deciding which residues to mutate requires knowledge of the characteristics they elicit. We probed the characteristics of residues in granulocyte-colony stimulating factor (G-CSF) using a thermal melt (from 295K to 323K) to denature it in a 700 MHz Bruker spectrometer. These characteristics included dynamics, micro-environmental changes experienced/ induced during denaturing and structure-function relationships. 15N-1H HSQC experiments were performed at 2K increments along with this thermal melt. We observed that dynamic residues that also undergo a lot of change in their microenvironment were predominantly in unstructured regions. Moreover, we were able to identify four residues (G4, A6, T133 and Q134) that we class as high priority targets for mutagenesis, given that they all appear in both the top 10% of measures for environmental changes and dynamics (∑Δ and ∆PI). We were also able to probe these NMR observables and combine them with molecular dynamics (MD) to elucidate what appears to be an opening motion of G-CSFs binding site III. V48 appears to be pivotal to this opening motion, which also seemingly distorts the loop region between helices A and B. This observation is in agreement with previous findings that the conformation of this loop region becomes altered in an aggregation-prone state of G-CSF. Hence, we present here an approach to profile the characteristics of residues in order to highlight their potential as rational mutagenesis targets and their roles in important conformational changes. These findings present not only an opportunity to effectively make biobetters, but also open up the possibility to further understand epistasis and machine learn residue behaviours.

Keywords: protein engineering, rational mutagenesis, NMR, molecular dynamics

Procedia PDF Downloads 147
1 Between Leader-Member Exchange and Toxic Leadership: A Theoretical Review

Authors: Aldila Dyas Nurfitri


Nowadays, leadership has became the one of main issues in forming organization groups even countries. The concept of a social contract between the leaders and subordinates become one of the explanations for the leadership process. The interests of the two parties are not always the same, but they must work together to achieve both goals. Based on the concept at the previous it comes “The Leader Member Exchange Theory”—well known as LMX Theory, which assumes that leadership is a process of social interaction interplay between the leaders and their subordinates. High-quality LMX relationships characterized by a high carrying capacity, informal supervision, confidence, and power negotiation enabled, whereas low-quality LMX relationships are described by low support, large formal supervision, less or no participation of subordinates in decision-making, and less confidence as well as the attention of the leader Application of formal supervision system in a low LMX behavior was in line with strict controls on toxic leadership model. Leaders must be able to feel toxic control all aspects of the organization every time. Leaders with this leadership model does not give autonomy to the staff. This behavior causes stagnation and make a resistant organizational culture in an organization. In Indonesia, the pattern of toxic leadership later evolved into a dysfunctional system that is growing rapidly. One consequence is the emergence of corrupt behavior. According to Kellerman, corruption is defined as a pattern and some subordinates behave lie, cheat or steal to a degree that goes beyond the norm, they put self-interest than the common good.According to the corruption data in Indonesia based on the results of ICW research on 2012 showed that the local government sector ranked first with 177 cases. Followed by state or local enterprises as much as 41 cases. LMX is defined as the quality of the relationship between superiors and subordinates are implications for the effectiveness and progress of the organization. The assumption of this theory that leadership as a process of social interaction interplay between the leaders and his followers are characterized by a number of dimensions, such as affection, loyalty, contribution, and professional respect. Meanwhile, the toxic leadership is dysfunctional leadership in organization that is led by someone with the traits are not able to adjust, do not have integrity, malevolent, evil, and full of discontent marked by a number of characteristics, such as self-centeredness, exploiting others, controlling behavior, disrespecting others, suppress innovation and creativity of employees, and inadequate emotional intelligence. The leaders with some characteristics, such as high self-centeredness, exploiting others, controlling behavior, and disrespecting others, tends to describe a low LMX relationships directly with subordinates compared with low self-centeredness, exploiting others, controlling behavior, and disrespecting others. While suppress innovation and creativity of employees aspect and inadequate emotional intelligence, tend not to give direct effect to the low quality of LMX.

Keywords: leader-member exchange, toxic leadership, leadership

Procedia PDF Downloads 419