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The enormous catalytic power of natural enzymes relies on the ability to overcome the bottleneck event in the enzymatic cycle, yet the underlying physical mechanisms are not fully understood. Here, by performing molecular simulations of the whole enzymatic cycle for a model multisubstrate enzyme with a dynamic energy landscape model, we show that multisubstrate enzymes can utilize steric frustration to facilitate the rate-limiting product-release step. During the enzymatic cycles, the bottleneck product is actively squeezed out by the binding of a new substrate at the neighboring site through the population of a substrate-product cobound complex, in which the binding pockets are frustrated due to steric incompatibility. Such steric frustration thereby enables an active mechanism of product release driven by substrate-binding energy, facilitating the enzymatic cycle.
This article was published in the following journal.
Name: Physical review letters
Nonsyndromic craniosynostosis (NSC) may manifest with complex behavioral, attentional, and emotional sequelae. We characterized higher-level brain connectivity in adolescent NSC patients in response t...
The problems of protein folding and protein design are two sides of the same coin. Protein folding involves exploring a protein's configuration space given a fixed sequence, while protein design invol...
Fluorine atom is the second smallest atom, nevertheless ortho-fluoro group may lead to stable N-aryl atropisomers when the steric demand of the flanking substituents is large enough. 2-Alkyl-3-(2-fluo...
Lignocellulosic biomass deconstruction is a bottleneck for obtaining biofuels and value-added products. Our main goal was to characterize the secretome of a novel isolate, Cellulomonas sp. B6, when gr...
The extensive number of metabolic processes regulated by phosphatidylinositol (PI) phospholipids highlights their physiological importance. The major metabolic pathway for their biosynthesis in cells ...
A new enzymatic assay was developed by NMD Diagnostics for rapid diagnosis of Enteroviral CNS infection. This study will compare this assay to RT-PCR, by testing human CSF samples taken fr...
The FOCUS program (study treatment) is an established evidence-based intervention whose redesign for families and couples dealing with serious and chronic illnesses will provide a creative...
In this short-term study a method for the evaluation of the metabolic competency of the urea cycle in vivo will be assessed. In order to monitor the efficacy of new treatment options for p...
This study will be conducted in different centres and will study adult patients with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL). The study treatment will inc...
RATIONALE: The urea cycle is the process in which nitrogen is removed from the blood and converted into urea, a waste product found in urine . Urea cycle disorders are inherited disorders ...
Personality trait related to tendency to respond to threat, frustration or a loss with negative emotions (e.g., ANGER; ANXIETY; FRUSTRATION; embarrassment and sadness).
Proteins which are involved in the phenomenon of light emission in living systems. Included are the "enzymatic" and "non-enzymatic" types of system with or without the presence of oxygen or co-factors.
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.
The motivational and/or affective state resulting from being blocked, thwarted, disappointed or defeated.
An acyclic state that resembles PREGNANCY in that there is no ovarian cycle, ESTROUS CYCLE, or MENSTRUAL CYCLE. Unlike pregnancy, there is no EMBRYO IMPLANTATION. Pseudopregnancy can be experimentally induced to form DECIDUOMA in the UTERUS.
Enzymes are proteins that catalyze (i.e., increase the rates of) chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical re...