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1rjx

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(New page: 200px<br /> <applet load="1rjx" size="450" color="white" frame="true" align="right" spinBox="true" caption="1rjx, resolution 2.3&Aring;" /> '''Human PLASMINOGEN CA...)
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Revision as of 16:58, 12 November 2007


1rjx, resolution 2.3Å

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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 with SO4 as ligand. Active as Plasmin, with EC number 3.4.21.7 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 Mon Nov 12 19:04:42 2007

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