6LPG

human VASH1-SVBP complex

6LPG の概要

• エントリーDOI: 10.2210/pdb6lpg/pdb
• 分子名称: Tubulinyl-Tyr carboxypeptidase 1, Small vasohibin-binding protein, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: tubulin carboxypeptidases, microtubule modification, angiogenesis, hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 37526.07

構造登録者

Ikeda, A.,Nishino, T. (登録日: 2020-01-10, 公開日: 2020-10-21, 最終更新日: 2023-11-29)

主引用文献

Ikeda, A.,Urata, S.,Ando, T.,Suzuki, Y.,Sato, Y.,Nishino, T.
The crystal structure of the tetrameric human vasohibin-1-SVBP complex reveals a variable arm region within the structural core.
Acta Crystallogr D Struct Biol, 76:993-1000, 2020

PubMed Abstract: Vasohibins regulate angiogenesis, tumor growth, metastasis and neuronal differentiation. They form a complex with small vasohibin-binding protein (SVBP) and show tubulin tyrosine carboxypeptidase activity. Recent crystal structure determinations of vasohibin-SVBP complexes have provided a molecular basis for complex formation, substrate binding and catalytic activity. However, the regulatory mechanism and dynamics of the complex remain elusive. Here, the crystal structure of the VASH1-SVBP complex and a molecular-dynamics simulation study are reported. The overall structure of the complex was similar to previously reported structures. Importantly, however, the structure revealed a domain-swapped heterotetramer that was formed between twofold symmetry-related molecules. This heterotetramerization was stabilized by the mutual exchange of ten conserved N-terminal residues from the VASH1 structural core, which was intramolecular in other structures. Interestingly, a comparison of this region with previously reported structures revealed that the patterns of hydrogen bonding and hydrophobic interactions vary. In the molecular-dynamics simulations, differences were found between the heterotetramer and heterodimer, where the fluctuation of the N-terminal region in the heterotetramer was suppressed. Thus, heterotetramer formation and flexibility of the N-terminal region may be important for enzyme activity and regulation.

PubMed: 33021501
DOI: 10.1107/S2059798320011298

実験手法

X-RAY DIFFRACTION (2.3 Å)