金属センサタンパク質のアロステリック経路における亜鉛媒介相互作用のエネルギー

Dhruva K Chakravorty¹, Trent M Parker, Alfredo J Guerra

¹Department of Chemistry and Quantum Theory Project, University of Florida, Gainesville, Florida 32611-8435, United States.

Journal of the American Chemical Society

|December 11, 2012

まとめ

亜鉛媒介の水素結合は,金属感知タンパク質のDNA結合に不可欠である. 反応部位でのより強い相互作用は,スイッチとして作用し,金属の存在にDNA結合をロックします.

科学分野:

バイオケミストリーバイオケミストリー
構造生物学構造生物学とは
コンピュータ生物学コンピュータ生物学

背景:

金属感知タンパク質は,DNAオペレータ結合のためのアロステリックメカニズムを使用します.
金属媒介のインタープロトーマー水素結合は,このアロステル調節の鍵です.

研究の目的:

ArsR/SmtBおよびMarRファミリータンパク質における亜鉛媒介相互作用のエネルギー研究.
特徴づけられていないアロステルタンパク質の形態に関する構造的洞察を提供する.
アロステル反応における金属媒介結合の役割を決定する.

主な方法:

タンパク質と金属の相互作用を研究するために,計算手法が採用されました.
亜鉛媒介の水素結合のエネルギー分析が行われました.
アポタンパク質 (金属なし) のシミュレーションが行われました.

主要な成果:

亜鉛媒介の相互作用は,反応しない部位と比較して,機能的なアロステル部位において著しく強い (∼8 kcal/mol).
これらの強い相互作用は,水素結合部位の乱れを克服する.
相互作用はスイッチとして作用し,金属結合時に弱いDNA結合構造を安定させます.

結論:

金属媒介の二次協調殻の水素結合は,アロステリックに反応する部位で機能的な役割が保たれています.
このメカニズムは,亜鉛感知型転写レギュレータに不可欠です.
この発見は,タンパク質アロステリーに関する新しい構造的洞察を提供します.

さらに関連する動画

11:04

Ion Mobility-Mass Spectrometry Techniques for Determining the Structure and Mechanisms of Metal Ion Recognition and Redox Activity of Metal Binding Oligopeptides

Published on: September 7, 2019

08:24

Using Mycobacterium smegmatis as a Bioindicator for Zinc-Limited Growth Conditions in Mycobacteria

Published on: September 20, 2024

関連する概念動画

01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...

00:49

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence the...

01:08

Allosteric Regulation

Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...

01:58

Cooperative Allosteric Transitions

Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...

01:13

Introduction to Mechanisms of Enzyme Catalysis

For many years, scientists thought that enzyme-substrate binding took place in a simple "lock-and-key" fashion. This model stated that the enzyme and substrate fit together perfectly in one instantaneous step. However, current research supports a more refined view scientists call induced fit. The induced-fit model expands upon the lock-and-key model by describing a more dynamic interaction between enzyme and substrate. As the enzyme and substrate come together, their interaction causes a mild...

01:26

EDTA: Auxiliary Complexing Reagents

EDTA titrations are usually carried out in highly basic conditions, where the fully deprotonated form of EDTA, Y4−, actively complexes with the free metal ions in the solution. Several metal ions precipitate as hydrous oxide (hydroxides, oxides, or oxyhydroxides) under these conditions, lowering the concentration of free metal ions in the solution. For this reason, auxiliary complexing agents or ligands such as ammonia, tartrate, citrate, or triethanolamine are used in EDTA titrations to...

関連する実験動画