Staphylokinase (SAK; also known as staphylococcal

fibrinolysin Fibrinolysin is an enzyme derived from plasma of bovine origin (plasmin) or extracted from cultures of certain bacteria. It is used locally only and exclusively together with the enzyme desoxyribonuclease (extracted from bovine pancreas). Fibrinol ...

or Müller's factor) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

produced by ''

Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posi ...

''. It contains 136 amino acid residues and has a molecular mass of 15kDa. Synthesis of staphylokinase occurs in late exponential phase. It is similar to

streptokinase Streptokinase is a thrombolysis, thrombolytic medication activating plasminogen by nonenzymatic mechanism. As a medication it is used to thrombolysis, break down clots in some cases of myocardial infarction (heart attack), pulmonary embolism, an ...

. Staphylokinase is positively regulated by the "agr" gene regulator. It activates

plasminogen Plasmin is an important enzyme () present in blood that degrades many blood plasma proteins, including fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein (in the zymogen form of plasminogen) is enco ...

to form plasmin, which digests

fibrin Fibrin (also called Factor Ia) is a fibrous protein, fibrous, non-globular protein involved in the Coagulation, clotting of blood. It is formed by the action of the protease thrombin on fibrinogen, which causes it to polymerization, polymerize. ...

clots. This disrupts the fibrin meshwork which forms to keep

infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...

s 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 the presence of fibrin, the inhibition is delayed, creating a unique mechanism for fibrin selectivity in plasma. Staphylokinase also cleaves

IgG Immunoglobulin G (IgG) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ant ...

and complement component

C3b C3b is the larger of two elements formed by the cleavage of complement component 3, and is considered an important part of the innate immune system. C3b is potent in opsonization: tagging pathogens, immune complexes (antigen-antibody), and apoptot ...

, inhibiting

phagocytosis Phagocytosis () is the process by which a cell (biology), cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs ph ...

Structure

The full length of mature staphylokinase

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...

is 489bp. The first 27

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

s code for a signal

peptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...

which is cleaved off in the mature protein (mSak). There is little or no homology between the

primary structure Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthe ...

of Sak and other plasminogen activators. The natural variants of Sak are Sak42D, SakφC and SakSTAR. These variants have four

nucleotide Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...

differences in the coding region with one

silent mutation Silent mutations, also called synonymous or samesense mutations, are mutations in DNA that do not have an observable effect on the organism's phenotype. The phrase ''silent mutation'' is often used interchangeably with the phrase '' synonymous mut ...

. The affected codons are amino acids 38, 61, 63 and 70 in the full length staphylokinase. Amino acid 38 is

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. Lysine contains an α-amino group (which is in the protonated form when the lysine is dissolved in water at physiological pH), an α-carboxylic acid group ( ...

, amino acid 61 is

serine Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − ...

in SaKSTAR,

glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (G ...

in SakφC, and

arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidinium, guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) a ...

in Sak42D. Amino acid 63 is glycine in SakSTAR and SakφC, but arginine in Sak42D. SakSTAR and SakφC amino acid 70 is

histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an Amine, α-amino group (which is in the protonated –NH3+ form under Physiological condition, biological conditions), a carboxylic ...

, whereas it is arginine in Sak42D. The mature structure of staphylokinase consists of 163 amino acids, and it is elongated in shape. Sak contains two folded domains which are of similar size. The distance from the center of gravity between the two domains is 3.7 nm. When in solution, this position varies between the two domains suggesting a flexible

dumbbell The dumbbell, a type of free weight, is a piece of equipment used in weight training. It is usually used individually and/or in pairs, with one in each hand. History The forerunner of the dumbbell, halteres, were used in ancient Greece as li ...

shape.

References

{{Portal bar, Biology, border=no EC 3.4.24 Staphylococcaceae Fibrinolytic enzymes

Structure

See also

References