1C77

STAPHYLOKINASE (SAK) DIMER

1C77 の概要

• エントリーDOI: 10.2210/pdb1c77/pdb
• 関連するPDBエントリー: 1c76 1c78 1c79
• 分子名称: STAPHYLOKINASE (1 entity in total)
• 機能のキーワード: beta-grasp family, hydrolase
• 由来する生物種: Staphylococcus aureus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 30975.17

構造登録者

Rao, Z.,Jiang, F.,Liu, Y.,Zhang, X.,Chen, Y.,Bartlam, M.,Song, H.,Ding, Y. (登録日: 2000-02-01, 公開日: 2000-08-01, 最終更新日: 2023-12-27)

主引用文献

Chen, Y.,Song, G.,Jiang, F.,Feng, L.,Zhang, X.,Ding, Y.,Bartlam, M.,Yang, A.,Ma, X.,Ye, S.,Liu, Y.,Tang, H.,Song, H.,Rao, Z.
Crystal structure of a staphylokinase: variant a model for reduced antigenicity.
Eur.J.Biochem., 269:705-711, 2002

PubMed Abstract: Staphylokinase (SAK) is a 15.5-kDa protein from Staphylococcus aureus that activates plasminogen by forming a 1 : 1 complex with plasmin. Recombinant SAK has been shown in clinical trials to induce fibrin-specific clot lysis in patients with acute myocardial infarction. However, SAK elicits high titers of neutralizing antibodies. Biochemical and protein engineering studies have demonstrated the feasibility of generating SAK variants with reduced antigenicity yet intact thrombolytic potency. Here, we present X-ray crystallographic evidence that the SAK(S41G) mutant may assume a dimeric structure. This dimer model, at 2.3-A resolution, could explain a major antigenic epitope (residues A72-F76 and residues K135-K136) located in the vicinity of the dimer interface as identified by phage-display. These results suggest that SAK antigenicity may be reduced by eliminating dimer formation. We propose several potential mutation sites at the dimer interface that may further reduce the antigenicity of SAK.

PubMed: 11856331
DOI: 10.1046/j.0014-2956.2001.02706.x

実験手法

X-RAY DIFFRACTION (2.3 Å)