1rjx
From Proteopedia
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| , resolution 2.3Å | |||||||
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| Ligands: | |||||||
| Gene: | PLG (Homo sapiens) | ||||||
| Activity: | Plasmin, with EC number 3.4.21.7 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human PLASMINOGEN CATALYTIC DOMAIN, K698M MUTANT
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Conjunctivitis, ligneous OMIM:[173350], Plasminogen Tochigi disease OMIM:[173350], Plasminogen deficiency, types I and II OMIM:[173350], Thrombophilia, dysplasminogenemic OMIM:[173350]
About this Structure
1RJX is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Characterization of Lys-698-to-Met substitution in human plasminogen catalytic domain., Terzyan S, Wakeham N, Zhai P, Rodgers K, Zhang XC, Proteins. 2004 Aug 1;56(2):277-84. PMID:15211511
Page seeded by OCA on Thu Mar 20 13:52:38 2008
