4JIX

Crystal structure of the metallopeptidase zymogen of Methanocaldococcus jannaschii jannalysin

4JIX の概要

• エントリーDOI: 10.2210/pdb4jix/pdb
• 関連するPDBエントリー: 4JIU
• 分子名称: Projannalysin, ZINC ION, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (7 entities in total)
• 機能のキーワード: hydrolase, metallopeptidase zymogen, minigluzincin
• 由来する生物種: Methanocaldococcus jannaschii
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 27999.34

構造登録者

Lopez-Pelegrin, M.,Cerda-Costa, N.,Martinez-Jimenez, F.,Cintas-Pedrola, A.,Canals, A.,Peinado, J.R.,Marti-Renom, M.A.,Lopez-Otin, C.,Arolas, J.L.,Gomis-Ruth, F.X. (登録日: 2013-03-07, 公開日: 2013-06-12, 最終更新日: 2024-03-20)

主引用文献

Lopez-Pelegrin, M.,Cerda-Costa, N.,Martinez-Jimenez, F.,Cintas-Pedrola, A.,Canals, A.,Peinado, J.R.,Marti-Renom, M.A.,Lopez-Otin, C.,Arolas, J.L.,Gomis-Ruth, F.X.
A novel family of soluble minimal scaffolds provides structural insight into the catalytic domains of integral membrane metallopeptidases
J.Biol.Chem., 288:21279-21294, 2013

PubMed Abstract: In the search for structural models of integral-membrane metallopeptidases (MPs), we discovered three related proteins from thermophilic prokaryotes, which we grouped into a novel family called "minigluzincins." We determined the crystal structures of the zymogens of two of these (Pyrococcus abyssi proabylysin and Methanocaldococcus jannaschii projannalysin), which are soluble and, with ∼100 residues, constitute the shortest structurally characterized MPs to date. Despite relevant sequence and structural similarity, the structures revealed two unique mechanisms of latency maintenance through the C-terminal segments previously unseen in MPs as follows: intramolecular, through an extended tail, in proabylysin, and crosswise intermolecular, through a helix swap, in projannalysin. In addition, structural and sequence comparisons revealed large similarity with MPs of the gluzincin tribe such as thermolysin, leukotriene A4 hydrolase relatives, and cowrins. Noteworthy, gluzincins mostly contain a glutamate as third characteristic zinc ligand, whereas minigluzincins have a histidine. Sequence and structural similarity further allowed us to ascertain that minigluzincins are very similar to the catalytic domains of integral membrane MPs of the MEROPS database families M48 and M56, such as FACE1, HtpX, Oma1, and BlaR1/MecR1, which are provided with trans-membrane helices flanking or inserted into a minigluzincin-like catalytic domain. In a time where structural biochemistry of integral-membrane proteins in general still faces formidable challenges, the minigluzincin soluble minimal scaffold may contribute to our understanding of the working mechanisms of these membrane MPs and to the design of novel inhibitors through structure-aided rational drug design approaches.

PubMed: 23733187
DOI: 10.1074/jbc.M113.476580

実験手法

X-RAY DIFFRACTION (2 Å)