SETドメインタンパク質メチルトランスファーゼの構造と触媒機構
Raymond C Trievel1, Bridgette M Beach, Lynnette M A Dirk
1Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Cell
|October 10, 2002
まとめ
研究者らは,Rubisco大サブユニットメチルトランスフェラーゼの構造を解明し,それがタンパク質をメチル化する方法を明らかにした. このメチル化プロセスは,遺伝子調節と植物代謝にとって極めて重要です.
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
- 酵素学 酵素学とは
背景:
- SETドメイン酵素によって触媒化されたタンパク質リジンメチル化は,クロマチンの構造,遺伝子静止,転写活性化,植物代謝を含む多様な生物学的プロセスにおいて重要な役割を果たします.
- これらの酵素の構造的基礎を理解することは,それらの調節機構の解読に不可欠です.
研究 の 目的:
- ルビスコの大型サブユニットメチルトランスフェラーゼの高解像度構造を決定する.
- この酵素によるメチル移転と基板認識のメカニズムを解明する.
主な方法:
- X線結晶学を用いて,2.6Aの解像度構造を得ました.
- 構造は,S-アデノシルホモシステインとHEPESイオンを含む擬似ビスブストラート複合体の構造を決定した.
主要な成果:
- 構造は,より大きなアルファヘリル型酵素折りの中に統合された,SETドメインの全ベータアーキテクチャを明らかにします.
- SETドメイン内の保存された領域は,S-アデノシルメチオニンと基板リシンのための2つの異なる結合部位を形成し,孔によって接続されています.
- 狭い孔にある保存されたチロシン残留物は,メチル転送を触媒化することを提案されています.
- コファクター (S-アデノシルメチオニン) は,基質結合部位とは異なる"バックドア"メカニズムを通じて活性部位に入ります.
結論:
- 構造的な洞察は,Rubiscoの大型サブユニットメチルトランスフェラーゼ活性に関するメカニズム的理解を提供します.
- 酵素の構造は,高度に特定のタンパク質の認識と,複数のメチル群の追加の可能性を容易にする.
- この研究は,タンパク質メチル化とその生物学的システムにおける規制的役割のより広範な理解に貢献します.
関連する概念動画
02:26Conservation of Protein Domains Over Different Proteins
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
01:13Introduction 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...
01:19Allosteric 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,...
00:59Mechanisms of Membrane Domain Formation
Different physical properties of lipids and proteins allow them to localize and form distinct islands or domains in the membrane. Some membrane domains are formed due to protein-protein interactions, whereas others are formed due to the presence of specific lipids such as sphingolipids and sterols—for example, large proteins, such as bacteriorhodopsin, aggregate and create distinct domains.
Another mechanism for membrane domain formation involves membrane proteins interacting with cytoskeletal...
Another mechanism for membrane domain formation involves membrane proteins interacting with cytoskeletal...
01:13Introduction 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...