Simulations Reveal Key Role of Arg15 for Promiscuous Activity in HisA Enzyme

Author(s):  
Kshatresh Dutta Dubey ◽  
Warispreet Singh

The HisA enzyme catalyzes the first step of histidine biosynthesis via Amadori rearrangement of substrate ProFAR. Since it possesses the most conserved and ancient TIM-barrel fold, it provides an ideal...

2018 ◽  
Vol 74 (1) ◽  
pp. 41-51
Author(s):  
Kazuhiro Yamada ◽  
Markos Koutmos

Methyl transfer between methyltetrahydrofolate and corrinoid molecules is a key reaction in biology that is catalyzed by a number of enzymes in many prokaryotic and eukaryotic organisms. One classic example of such an enzyme is cobalamin-dependent methionine synthase (MS). MS is a large modular protein that utilizes an SN2-type mechanism to catalyze the chemically challenging methyl transfer from the tertiary amine (N5) of methyltetrahydrofolate to homocysteine in order to form methionine. Despite over half a century of study, many questions remain about how folate-dependent methyltransferases, and MS in particular, function. Here, the structure of the folate-binding (Fol) domain of MS fromThermus thermophilusis reported in the presence and absence of methyltetrahydrofolate. It is found that the methyltetrahydrofolate-binding environment is similar to those of previously described methyltransferases, highlighting the conserved role of this domain in binding, and perhaps activating, the methyltetrahydrofolate substrate. These structural studies further reveal a new distinct and uncharacterized topology in the C-terminal region of MS Fol domains. Furthermore, it is found that in contrast to the canonical TIM-barrel β8α8fold found in all other folate-binding domains, MS Fol domains exhibit a unique β8α7fold. It is posited that these structural differences are important for MS function.


JAMA ◽  
1966 ◽  
Vol 195 (12) ◽  
pp. 1005-1009 ◽  
Author(s):  
D. J. Fernbach
Keyword(s):  

JAMA ◽  
1966 ◽  
Vol 195 (3) ◽  
pp. 167-172 ◽  
Author(s):  
T. E. Van Metre

2018 ◽  
Vol 41 ◽  
Author(s):  
Winnifred R. Louis ◽  
Craig McGarty ◽  
Emma F. Thomas ◽  
Catherine E. Amiot ◽  
Fathali M. Moghaddam

AbstractWhitehouse adapts insights from evolutionary anthropology to interpret extreme self-sacrifice through the concept of identity fusion. The model neglects the role of normative systems in shaping behaviors, especially in relation to violent extremism. In peaceful groups, increasing fusion will actually decrease extremism. Groups collectively appraise threats and opportunities, actively debate action options, and rarely choose violence toward self or others.


2018 ◽  
Vol 41 ◽  
Author(s):  
Kevin Arceneaux

AbstractIntuitions guide decision-making, and looking to the evolutionary history of humans illuminates why some behavioral responses are more intuitive than others. Yet a place remains for cognitive processes to second-guess intuitive responses – that is, to be reflective – and individual differences abound in automatic, intuitive processing as well.


2020 ◽  
Vol 43 ◽  
Author(s):  
Stefen Beeler-Duden ◽  
Meltem Yucel ◽  
Amrisha Vaish

Abstract Tomasello offers a compelling account of the emergence of humans’ sense of obligation. We suggest that more needs to be said about the role of affect in the creation of obligations. We also argue that positive emotions such as gratitude evolved to encourage individuals to fulfill cooperative obligations without the negative quality that Tomasello proposes is inherent in obligations.


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