メチルグリオキサール合成酵素とトリオフォスファートイソメラーゼの機能的特異性:QM/MM分析を組み合わせた解析
Xiaodong Zhang1, David H T Harrison, Qiang Cui
1Department of Chemistry and Theoretical Chemistry Institute, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706, USA.
Journal of the American Chemical Society
|December 12, 2002
まとめ
計算分析により,トリオフォスファートイソメラーゼ (TIM) とメチルグリオキサール合成酵素 (MGS) の酵素特異性の違いが明らかになりました. MGSは,触媒基底の不柔軟性によって製品形成を防ぐが,TIMは触媒基底の不柔軟性を防ぐ.
科学分野:
- バイオケミストリー バイオケミストリー
- コンピューティング・ケミストリー
- 酵素学 酵素学とは
背景:
- トリオホスファートイソメラーゼ (TIM) とメチルグリオキサール合成酵素 (MGS) は,同じ基板である二酸化酸化アセトン酸塩 (DHAP) を処理する類似の活性部位を持つ酵素です.
- TIMはDHAPのイソメリゼーションをグリセルアルデヒド3リン酸 (GAP) に触媒化し,MGSはDHAPからのリン酸除去を触媒化する.
研究 の 目的:
- TIMとMGSの機能的特異性の分子起源を解明する.
- 基板と活性部位の類似性にもかかわらず,これらの酵素の独特の触媒活動を支配する要因を調査する.
主な方法:
- 組み合わせた量子力学/分子力学 (QM/MM) 計算,特にSCC-DFTB/CHARMMが採用されました.
- 分析は,アクティブサイトの柔軟性,静電的貢献,ステレオエレクトロニック要因に焦点を当てた.
主要な成果:
- GAP形成は,TIM (Glu 165) と比較して,その触媒基 (Asp 71) の柔軟性が低下したため,MGSで抑制されます.
- タンパク質と水分子の静電相互作用は,TIMにおけるリン酸除去を抑制するためにステレオ電子的要因よりも重要である.
結論:
- 酵素の機能的特異性は,触媒ベース柔軟性 (MGS) と静電環境 (TIM) の違いから生じる.
- TIMのリン酸除去抑制のための確立されたステレオエレクトロニックの論証は,以前考えられていたよりも少ない.
さらに関連する動画
17:12Profiling of Methyltransferases and Other S-adenosyl-L-homocysteine-binding Proteins by Capture Compound Mass Spectrometry (CCMS)
Published on: December 20, 2010
05:57Synthesizing Amino Acids Modified with Reactive Carbonyls in Silico to Assess Structural Effects Using Molecular Dynamics Simulations
Published on: April 26, 2024
関連する概念動画
01:19Allosteric 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,...
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,...
01:15Mass Spectrometry of Amines
In mass spectroscopy, amines undergo fragmentation to give parent ions with odd molecule weights. This observed mass spectrum follows the nitrogen rule; a molecule with an odd number of nitrogen atoms produces a molecular ion with an odd molecular weight. Amines undergo fragmentation through α cleavage, producing nitrogen-containing cations—iminium ions—and alkyl radicals. Mass spectra of aromatic and cyclic aliphatic amines exhibit strong molecular ion peaks, but acyclic aliphatic amines show...
00:55Mass Spectrometry: Amine Fragmentation
Amines can be identified using mass spectroscopy based on their characteristic fragmentation patterns. The molecular ions of amines undergo fragmentation via ⍺-cleavage. The ⍺-cleavage of the carbon-carbon bonds in amines generates an alkyl radical and resonance-stabilized nitrogen-containing cation.
In amines, the number of nitrogen atoms affects the mass of the molecular ion, which is described by the nitrogen rule of mass spectrometry. This rule states that a compound containing a single or...
In amines, the number of nitrogen atoms affects the mass of the molecular ion, which is described by the nitrogen rule of mass spectrometry. This rule states that a compound containing a single or...