1RJX

Human PLASMINOGEN CATALYTIC DOMAIN, K698M MUTANT

Summary for 1RJX

• Entry DOI: 10.2210/pdb1rjx/pdb
• Related: 1DDJ 1L4D 1L4Z 1QRZ
• Descriptor: Plasminogen, SULFATE ION (3 entities in total)
• Functional Keywords: microplasminogen, plasminogen activation, streptokinase, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P00747
• Total number of polymer chains: 1
• Total formula weight: 27805.57

Authors

Terzyan, S.,Wakeham, N.,Zhai, P.,Rodgers, K.,Zhang, X.C. (deposition date: 2003-11-20, release date: 2003-12-02, Last modification date: 2024-10-30)

Primary citation

Terzyan, S.,Wakeham, N.,Zhai, P.,Rodgers, K.,Zhang, X.C.
Characterization of Lys-698 to met substitution in human plasminogen catalytic domain
Proteins, 56:277-284, 2004

PubMed Abstract: Streptokinase (SK) is a human plasminogen (Pg) activator secreted by streptococci. The activation mechanism of SK differs from that of physiological Pg activators in that SK is not a protease and cannot proteolytically activate Pg. Instead, it forms a tight complex with Pg that proteolytically activates other Pg molecules. The residue Lys-698 of human Pg was hypothesized to participate in triggering activation in the SK-Pg complex. Here, we report a study of the Lys-698 to Met substitution in the catalytic domain of Pg (microPg) containing the proteolytic activation-resistant background (R561A). While it remains competent in forming a complex with SK, maintaining a comparable equilibration dissociation constant (K(D)), the recombinant protein shows a nearly 60-fold reduction in amidolytic activity relative to its R561A background when mixed with native SK. A 2.3 A crystal structure of this mutant microPg confirmed the correct folding of this recombinant protein. Combined with other biochemical data, these results support the premise that Lys-698 of human Pg plays a functional role in the so-called N-terminal insertion activation mechanism by SK.

PubMed: 15211511
DOI: 10.1002/prot.20070

Experimental method

X-RAY DIFFRACTION (2.3 Å)