1C78

STAPHYLOKINASE (SAK) DIMER

Summary for 1C78

• Entry DOI: 10.2210/pdb1c78/pdb
• Related: 1c76 1c77 1c79
• Descriptor: STAPHYLOKINASE (1 entity in total)
• Functional Keywords: beta-grasp family, hydrolase
• Biological source: Staphylococcus aureus
• Total number of polymer chains: 2
• Total formula weight: 30975.17

Authors

Rao, Z.,Jiang, F.,Liu, Y.,Zhang, X.,Chen, Y.,Bartlam, M.,Song, H.,Ding, Y. (deposition date: 2000-02-01, release date: 2000-08-01, Last modification date: 2023-12-27)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.3 Å)