1ssn
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(New page: 200px<br /><applet load="1ssn" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ssn" /> '''STAPHYLOKINASE, SAKSTAR VARIANT, NMR, 20 STR...)
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Revision as of 00:30, 21 November 2007
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STAPHYLOKINASE, SAKSTAR VARIANT, NMR, 20 STRUCTURES
Overview
Staphylokinase, a 15.5 kDa protein from Staphylococcus aureus, is a, plasminogen activator which is currently undergoing clinical trials for, the therapy of myocardial infarction and peripheral thrombosis. The, three-dimensional (3D) NMR solution structure has been determined by, multidimensional heteronuclear NMR spectroscopy on uniformly 15N- and, 15N,13C-labeled samples of staphylokinase. Structural constraints were, obtained from 82 3JHNH alpha as well as 22 3JNH beta scalar coupling, constants and 2345 NOE cross-peaks, derived from 15N-edited and 13C-edited, 3D NOE spectra. NOE cross-peak assignments were confirmed by analysis of , inverted question mark15N,13C inverted question mark-edited and inverted, question mark13C,13C inverted question mark-edited 4D NOE spectra. The, structure is presented as a family of 20 conformers which show an average, rmsd of 1.02 +/- 0.15 A from the mean structure for the backbone atoms., The tertiary structure of staphylokinase shows a well-defined global, structure consisting of a central 13-residue alpha-helix flanked by a, two-stranded beta-sheet, both of which are located above a five-stranded, beta-sheet. Two of the connecting loops exhibit a higher conformational, heterogeneity. Overall, staphylokinase shows a strong asymmetry of, hydrophilic and hydrophobic surfaces. The N-terminal sequence, including, Lys10 which is the site of the initial proteolytic cleavage during, activation of plasminogen, folds back onto the protein core, thereby, shielding amino acids with functional importance in the plasminogen, activation process. From a comparison of the structure with mutational, studies, a binding region for plasminogen is proposed.
About this Structure
1SSN is a Single protein structure of sequence from Staphylococcus aureus. Full crystallographic information is available from OCA.
Reference
Nuclear magnetic resonance solution structure of the plasminogen-activator protein staphylokinase., Ohlenschlager O, Ramachandran R, Guhrs KH, Schlott B, Brown LR, Biochemistry. 1998 Jul 28;37(30):10635-42. PMID:9692953
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