Staphylokinase

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Staphylokinase
Identifiers
EC number 3.4.24.29
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum

Staphylokinase (SAK) is an amino acid enzyme from Staphylococcus aureus. It contains 136 amino acid residues and is a 15kDa protein. Growth of Staphylokinase is seen in late exponential phase.[1]

It is positively regulated by the "agr" gene regulator. It activates plasminogen to form plasmin, which digest fibrin clots. This disrupts the fibrin meshwork which can often form to keep an infection localized. Staphylokinase interacts with plasminogen to form a 1:1 complex that exposes the active site of the plasminogen molecule. The plasmin Sak complex is neutralized by α2- antiplasmin in plasma in the absence of fibrin, resulting in lysis. However, in presence of fibrin, the inhibition is delayed, creating a unique mechanism for fibrin selectivity in plasma.[2]

Staphylokinase also cleaves IgG and complement component C3b, inhibiting phagocytosis.

It is classified under EC 3.4.24.29, (formerly EC 3.4.99.22).

Structure[edit]

The full length, mature Staphylokinase mRNA is 489bp. The first 27 amino acid codes for a signal peptide which is cleaved off in the mature protein (mSak). There is little or no homology between primary structure of Sak and other plasminogen activators. The natural variants of Sak are Sak42D, SakφC and SakSTAR. These variants had four nucleotide differences in coding region with one silent mutation. The affected codons are amino acid at 38, 61, 63 and 70 in full length staphylokinase. Amino acid 38 is Lys , 61 is Ser in SaKSTAR and Gly in SakφC and Arg in Sak42D. Amino acid 63 is Gly in Sak STAR and SakφC but Arg in Sak42D. SakSTAR and SakφC amino acid 70 is His whereas Arg in Sak42D.[3][4]

The mature structure of staphylokinase consists of 163 amino acids. In solution the protein structure was analyzed by X-ray scattering, dynamic light scattering, ultracentrifugation and UV circular dichroism spectroscopy. Through these methods the radius of gyration 2. 3 nm, a stroke radius 2.1 nm and dimension maximum of 10 nm was obtained which indicated that the shape of staphylokinase is elongated. Sak contains two folded domains which are of similar size. The distance from the center of gravity between two domains is 3.7 nm and when in solution the position varies between two domains which state the shape of flexible dumbbell.[2]


References

  1. ^ Bokarewa MI, Jin T, Tarkowski A (2006). "Staphylococcus aureus: Staphylokinase". The International Journal of Biochemistry & Cell Biology. 38 (4): 504–509. doi:10.1016/j.biocel.2005.07.005. PMID 16111912. 
  2. ^ a b Rao S, Kumar A, Peravali JB, Ram KS, Pulicherla KK (2013). "Staphylokinase: a Boon in Medical Sciences". Mintage Journal of Pharmaceutical and Medical Sciences. 2 (2): 28–34. 
  3. ^ Collen D, Lijnen HR (1994). "Staphylokinase, a fibrin-specific plasminogen activator with therapeutic potential?" (PDF). Blood. 84 (3): 680–686. PMID 7519069. 
  4. ^ Vanderschueren S, Van de Werf F, Collen D (August 1997). "Recombinant staphylokinase for thrombolytic therapy". Fibrinolysis and Proteolysis. 11: 39–44. doi:10.1016/S0268-9499(97)80069-0.