タンパク質に対するCORM-3の反応性: Ru(II) 二カルボニル-リゾ酵素複合体の結晶構造
Teresa Santos-Silva1, Abhik Mukhopadhyay, João D Seixas
1REQUIMTE-CQFB, Departamento de Química, FCT-UNL, 2829-516 Caparica, Portugal.
Journal of the American Chemical Society
|January 6, 2011
まとめ
CORM-3は一酸化炭素を放出し,タンパク質と結合し,安定したルテニウム添加物を形成します. この研究は,CORM-3タンパク質結合に関与する特定の分子相互作用と調整部位を明らかにしています.
科学分野:
- バイオ・オーガニック化学 バイオ・オーガニック化学
- メタロタンパク質化学 メタロタンパク質化学
- ドラッグ・ディスカバリー・ディスカバリー・ドラッグ・ディスカバリー・ドラッグ・ディスカバリー
背景:
- 一酸化炭素放出分子 (CORM) は,生物系における一酸化炭素 (CO) の制御された放出に使用されます.
- CORM-3,[fac-Ru(CO)(3)Cl(κ(2)-H(2)NCH(2)CO(2)) は,生体内でのCOの供給のためのCORMとして知られています.
研究 の 目的:
- CORM-3とタンパク質の分子相互作用を解明する.
- その結果生じるルテニウムタンパク質添加物とその協調化学を特徴づける.
主な方法:
- インダクティブカップリングされたプラズマ-原子放射スペクトロスコーピー (ICP-AES)
- 液体染色体質量スペクトロメトリー (LC-MS)
- 赤外線スペクトロスコーピ (IR)
- X線結晶グラフィーです.
主要な成果:
- CORM-3は解離し,タンパク質との相互作用により,塩化物,グリシネート,および1つのCOリガンドを失います.
- 安定したアダクトは,タンパク質と残りのシス-Ru (II) (CO) (II) 断片の間に形成されます.
- X線結晶学により,鶏卵白のリゾ酵素に3つのルテニウム調整部位が特定され,主な部位は80%の占有率でファック-[His15) Ru (CO) (His15) Ru (CO) (His15) Ru (CO) (His15) Ru (His15) Ru (CO) (His15) Ru (CO) (His15) Ru (CO) (His15) Ru (CO) (His15) Ru (His15) Ru (CO) (His15) Ru (His15) Ru (His15) Ru (CO) (His15) Ru (His15) Ru (His15) Ru (His15) Ru (His15) Ru (His15) Ru (His15) Ru (His15) Ru (CO) (His15) Ru (His15) Ru (His15) Ru (His15) Ru (His15) Ru (His15) Ru (H15)) (H15)) (H15) (H15) (H15) (H15) (H15) (H15) (H15) (H15) (H15) (H15) (H15) (H1 (H15)) (H1 (H1 (H15)) (H1 (H1
結論:
- この研究は,CORM-3-タンパク質相互作用の最初の詳細な構造的および化学的特徴を提供します.
- これらのアダクトを理解することは,CORMの治療的応用と新しい金属薬の設計において極めて重要です.
関連する概念動画
Crystal Field Theory - Octahedral Complexes
Crystal Field Theory
To explain the observed behavior of transition metal complexes (such as colors), a model involving electrostatic interactions between the electrons from the ligands and the electrons in the unhybridized d orbitals of the central metal atom has been developed. This electrostatic model is crystal field theory (CFT). It helps to understand, interpret, and predict the colors, magnetic behavior, and some structures of coordination compounds of transition metals.
CFT focuses on...
To explain the observed behavior of transition metal complexes (such as colors), a model involving electrostatic interactions between the electrons from the ligands and the electrons in the unhybridized d orbitals of the central metal atom has been developed. This electrostatic model is crystal field theory (CFT). It helps to understand, interpret, and predict the colors, magnetic behavior, and some structures of coordination compounds of transition metals.
CFT focuses on...
Protein Organization
Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence.
The primary structure of a protein is its amino acid sequence.
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...
Globular and Fibrous Proteins
Many proteins can be classified into two distinct subtypes - globular or fibrous. These two types differ in their shapes and solubilities.
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...
Gene Families
Gene families consist of groups of genes proposed to have originated from a common ancestor. Typically these arise through events in which a gene or genes are mistakenly duplicated during cell division. Unlike their parent genes (which are subject to selection pressure to maintain function), these gene copies do not need to preserve their sequences and may evolve at a relatively faster rate.
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
Protein Folding
Overview


