ラッソペプチドイソペプチダゼの構造 糸状基質の処理のためのトポロジーを特定する
Jonathan R Chekan1,2, Joseph D Koos1,2, Chuhan Zong1,2
1Department of Biochemistry, ‡Institute for Genomic Biology and §Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign , 600 South Mathews Avenue, Urbana, Illinois 61801, United States and.
Journal of the American Chemical Society
|December 22, 2016
まとめ
研究者らは,ラッソペプチドイソペプチダゼの構造と機能を明らかにし,そのユニークな構造と基板認識機構を明らかにした. この発見は,ゲノムマイニングを通じて新しい生物活性ラッソペプチドを特定するのに役立ちます.
科学分野:
- 生物化学
- 構造生物学
- 分子生物学
背景:
- ラッソペプチドは,異ペプチド結合によって形成されるユニークな糸状の結び目構造を持つ生物活性分子である.
- いくつかのラッソペプチド生物合成クラスターには,この結合を水分解して線形ペプチドを生成する酵素,イソペプチダースが含まれています.
研究 の 目的:
- ラッソペプチドイソペプチダゼの構造を決定し,その作用機構を理解する.
- イソペプチダスがラッソペプチド基板を認識し処理する方法を調査する.
- 新しいラッソペプチド群を特定するためのゲノムマイニング戦略を開発する.
主な方法:
- X線結晶学を使用して,イソペプチダースの2. 4 Å解像度構造と基板の2.2 Å解像度コクリスタル構造を決定した.
- 酵素と基板の相互作用を調査するために,構造に基づく変異分析が行われました.
- ネットワークベースのゲノムマイニングは,イソペプチダース遺伝子の配列を使用して採用されました.
- 特定された生物合成クラスタを検証するために,異質表現を用いた.
主要な成果:
- ラッソペプチドイソペプチダゼは新しいディドメイン構造 (β-プロペラとα/βヒドロラーゼ) を有する.
- 同結晶化により,基質の変形と活性部位の再編成が明らかになり,同ペプチド結合の水解が容易になりました.
- ラッソペプチドの酵素認識は,配列の特異性ではなく,形状の互換性に基づいています.
- ゲノム・マイニングで 87のラッソ・ペプチド・クラスターが特定され,65は以前は記述されていなかった.
- 異質表現は,2つの特定されたクラスターからラッソペプチドの生成を確認した.
結論:
- 決定された構造は,ラッソペプチドイソペプチダースの触媒機構の洞察を提供します.
- 酵素の形状認識メカニズムは 機能に不可欠です
- 開発されたゲノムマイニング戦略は,新しいラッソペプチド生物合成クラスタを発見するのに有効であり,これらの生物活性分子に関する既知の多様性を拡大します.
関連する概念動画
The Proteasome Structure
2.0K
The ubiquitin-proteasome pathway is a well-known mechanism utilized by eukaryotic cells to remove cytoplasmic proteins that are misfolded, damaged, or no longer needed. In this pathway, the protein that needs to be eliminated undergoes a process called ubiquitination, where a chain of ubiquitin molecules is attached to the 48th lysine residue of the target protein. This ubiquitin modification helps the proteasome distinguish between a target protein and a healthy protein.
The proteasome is an...
The proteasome is an...
2.0K
Peptide Bonds
85.3K
A peptide bond covalently attaches amino acids through a dehydration reaction. One amino acid's carboxyl group and another amino acid's amino group combine, releasing a water molecule. The resulting bond is the peptide bond. The products that such linkages form are peptides. As more amino acids join this growing chain, the resulting chain is a polypeptide. Each polypeptide has a free amino group at one end. This end has the N-terminal, or the amino-terminal, and the other end has a free...
85.3K
Protein Digestion
112.5K
Protein digestion begins in the stomach, where the highly acidic environment can easily disrupt protein structure by exposing the peptide bonds of polypeptide chains. After polypeptide chains are broken into individual amino acids by a series of digestive enzymes, the amino acids are transported to the liver via the bloodstream to produce energy.
112.5K
The Proteasome
10.4K
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
10.4K
The Proteasome
1.9K
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
1.9K
Peptide Identification Using Tandem Mass Spectrometry
8.7K
Tandem mass spectrometry, also known as MS/MS or MS2, is an analytical technique that employs two mass analyzers. Essentially it is a series of mass spectrometers that helps isolate a particular biomolecule and then helps study its chemical properties.
This technique helps gather information regarding the protein from which the peptide was obtained and to study the peptides’ amino acid sequence. Identifying peptides from a complex mixture is an important component of the growing field of...
This technique helps gather information regarding the protein from which the peptide was obtained and to study the peptides’ amino acid sequence. Identifying peptides from a complex mixture is an important component of the growing field of...
8.7K


