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PubMed1987

Use of streptokinase for the salvage of a free flap: case report and review of the use of thrombolytic therapy.

This is the first case report of the clinical use of intraoperative streptokinase to promote free flap salvage. A latissimus dorsi free flap was mobilized to cover a scalping type injury. After 4 1/2 hours of ischemia and recurrent thrombosis, streptokinase was perfused into the thoracodorsal artery (7,500 units of streptokinase in 30 cc of normal saline). The free flap was exposed to this concentration of streptokinase for 10 minutes followed by drainage of the venous effluent in order to avoid possible deleterious systemic effects of the streptokinase. Good flow throughout the free flap resulted, and the flap remained viable, providing good coverage for the patient's skull. Controversies regarding the no-reflow phenomena and the use of various thrombolytic agents are discussed.

Aged↗

PubMed2006

Enhancement of recombinant streptokinase production in Lactococcus lactis by suppression of acid tolerance response.

Lactococcus lactis is a potential host for production of recombinant proteins, especially of therapeutic importance. However, in glucose-grown cultures, lowering of pH due to accumulation of lactic acid and the concomitant induction of acid tolerance response (ATR) may affect the recombinant protein produced. In this work, we have analyzed the effect of culture pH and the associated ATR on production of recombinant streptokinase. Streptokinase gene was cloned and expressed as a secretory protein in L. lactis under the control of P170 promoter. It was found to undergo degradation to form inactive products leading to low productivity. The extent of degradation and productivity of streptokinase was greatly influenced by the development of ATR, which was dependent on the pH of the culture and initial phosphate concentration of the medium. It was found that high pH and high initial phosphate concentration leads to suppression of ATR and this results in at least 2.5-fold increase in streptokinase productivity and significant decrease in degradation of streptokinase.

Adaptation, Physiological↗

PubMed1984

Combined intracoronary streptokinase infusion and coronary angioplasty during acute myocardial infarction.

PTCA was performed in 28 patients with acute MI immediately after intracoronary streptokinase administration. Indications were failure to obtain reflow in 16 patients and high-grade residual stenosis in 12. PTCA was successful in 11 of 16 cases of streptokinase failure, increasing the overall reflow rate from 66% to 77%. PTCA reduced residual coronary stenosis by more than 20% in 9 of 12 cases in which streptokinase infusion was successful, with 1 acute reocclusion. The frequency of recurrent ischemic events in hospital was 76% in patients with a stenosis of 90% or greater after streptokinase infusion (no PTCA), 14% when residual stenosis was less than 90%, and 6% after successful PTCA. Late restenosis or reocclusion was documented in 5 of 11 PTCA cases (45%). Immediate PTCA after streptokinase administration produces increased clinical stability in hospital, but late restenosis is frequent.

Angioplasty, Balloon↗

PubMed1988

Nuclear magnetic resonance and radionuclide angiographic assessment of acute myocardial infarction in a randomized trial of intravenous streptokinase.

Sixty-six patients presenting with their first evolving transmural acute myocardial infarction (AMI) were randomized to receive either streptokinase (n = 41) or placebo therapies (n = 25) within 6 hours of the onset of chest pain. These patients then underwent supine rest, exercise and after-nitroglycerin radionuclide angiography 3 weeks after AMI. Nuclear magnetic resonance (NMR) imaging was performed at 3 weeks as a more direct estimate of AMI size. Although peak creatine kinase values were comparably elevated between groups (2,367 +/- 1,486 IU/liter for streptokinase vs 2,637 +/- 1,305 IU/liter for placebo), there was a significant reduction in NMR-measured AMI size in the streptokinase group (3 +/- 2% of left ventricular volume vs 10 +/- 4% in the placebo group, p less than 0.05). This occurred despite comparable resting (54 +/- 11 vs 47 +/- 10% and exercise (53 +/- 12 vs 49 +/- 11%) global ejection fractions. However, following nitroglycerin, there was an improvement in global ejection fraction in the streptokinase-treated group that was not observed with placebo (61 +/- 13 vs 48 +/- 10%, p less than 0.05). A similar pattern was also observed with regional functional analysis. Thus, streptokinase therapy leads to a significant reduction in NMR-measured AMI size and to a greater degree of reversible left ventricular dysfunction.

Adult↗

PubMed1990

A double-blind randomized multicenter dose-ranging trial of intravenous streptokinase in acute myocardial infarction.

Intravenous streptokinase administration is now a widely applied therapy for patients in the early hours of acute myocardial infarction (AMI). The dosages used do not appear to be based on comparative clinical investigations. Therefore a double-blind randomized trial was carried out to establish the optimal dose of streptokinase. A total of 189 patients who had symptoms of AMI for less than 4 hours were treated with 200,000, 750,000, 1,500,000 or 3,000,000 IU streptokinase intravenously. At coronary angiography 2.8 +/- 2.7 hours (mean +/- standard deviation) after the start of streptokinase infusion, patency of the infarct-related coronary artery was observed in 38, 75, 60 and 82% of the patients, respectively, in the 4 groups. The result of the dosage of 200,000 IU was significantly poorer than that of the other dosages (p less than 0.01). The result of a dosage of 3,000,000 IU was significantly better than that of 1,500,000 IU (p less than 0.05), but the differences with 750,000 IU were not significant. Blood transfusion was required in 4 patients (2%), distributed over the 4 groups in 0, 2, 1 and 1 of the patients. One patient had major bleeding; this patient had been treated with 750,000 IU. The 3-month mortality-rate in the whole study population was 5%. Thus, of the 4 doses of streptokinase tested, 750,000 IU is the minimal therapeutic dosage, and the arguments for 1,500,000 IU as standard therapy for comparison with other fibrinolytic drugs are poor. The best results in this study were achieved with 3,000,000 IU, but further research will be needed to establish the efficacy and safety of this new regimen.

Aged↗

PubMed1986

Selective management of arterial occlusion with low-dose streptokinase.

Fibrinolytic therapy has been reported as a limited aid in limb salvage. It is allegedly fraught with complications and pitfalls; however, the usage of low-dose streptokinase has never totally been explored. The purpose of this study was to examine the role of low-dose streptokinase in arterial occlusion. Nineteen patients (12 men and 7 women) with an average age of 68 years (range 37 to 79 years) and a total of 22 limbs under study were treated with low-dose streptokinase (initial intravenous dose of 10,000 units and a subsequent dose of 5,000 to 10,000 units/hour) for 1 to 3 days. Seven of the patients underwent further operative intervention and four underwent angioplasty. Seven patients had diabetes controlled by insulin. Results were assessed clinically by angiography and by noninvasive measurement of distal pressure. Within 30 days of low-dose streptokinase therapy, four patients died from a myocardial infarction that was thought to be part of their total disease process. Limited salvage occurred in 19 of 22 limbs at risk. Ten patients (12 extremities) underwent subsequent balloon angioplasty or bypass surgery. There were three amputations. One patient received a below-knee amputation rather than an expected above-knee amputation, one had a below-knee amputation, and one had an above-knee amputation. In all cases, the patency or lack thereof was confirmed by angiography. The mean ankle to brachial pressure indices increased from 0.07 +/- 0.15 to 0.64 +/- 0.14 after therapy. There were no prolonged hospital stays due to complications in any of the patients. Selective infusions of low-dose streptokinase lyse thrombi, open collaterals, and provide an opportunity for extended surgery and angioplasty, increasing limb salvage without the risks of coagulopathy and bleeding that may occur in full-dose thrombolysis.

Adult↗

PubMed1991

Use of purified streptokinase in empyema and hemothorax.

Enzymatic debridement of the pleural cavity for retained hemothorax or empyema is a frequently overlooked option. Thirteen of fourteen patients (93%) with retained pleural collections underwent successful enzymatic debridement and tube drainage with purified streptokinase injections. The average increase in chest tube output following streptokinase injections was 158%. No significant adverse reactions occurred. One patient required thoracotomy when streptokinase therapy failed. Two others had successful resolution of their pleural collections but required thoracotomy for other indications. There were two deaths (14%), which were unrelated to the use of streptokinase or residual empyema. Intrapleural streptokinase is a safe, effective means of removing retained proteinaceous collections in the pleural space. It is a useful adjunct to chest tube drainage and may obviate the need for more invasive procedures.

Adult↗

PubMed1990

Antistreptokinase titres after intravenous streptokinase.

Streptokinase neutralisation titres were measured in a series of 25 patients who received streptokinase for the treatment of acute myocardial infarction. Before treatment, neutralisation titres were low (0.3 X 10(6) neutralisation units or less) in all patients. 3 months after treatment, neutralisation titres in 24 were such that a typical therapeutic dose of 1.5 million units of streptokinase would have been fully neutralised. At 4 1/2-8 1/2 months, 18 of 20 patients had neutralisation titres such that at least 50% of a dose of 1.5 million units of streptokinase would have been neutralised. After 8 months, neutralisation titres ranged from 0.4 to 2.0 million units in 8 patients. A decision to readminister streptokinase within 8 months (and probably up to 1 year) of previous thrombolytic treatment should take account of the neutralising capacity of plasma and the dose should be adjusted accordingly.

Antibodies↗

PubMed1992

At least five antigenic epitopes on the streptokinase molecule are recognized by human CD4+ TCR alpha beta+ T cells.

The streptokinase molecule (415 AA) was cleaved at methionine 237, 347 and 370 yielding four polypeptide fragments. Human HLA-class II restricted streptokinase-specific T cell clones and cell lines (CD2+, CD3+, CD4+, CD8-, TCR alpha beta+, TCR gamma delta-) recognized antigenic epitopes on all four fragments AA 1-236, AA 238-346, AA 348-369 and AA 371-415. T cell clones recognizing fragment AA 1-236 were restricted by at least two different HLA-class II elements, this indicating that more than one antigenic epitope can be recognized on this fragment. In addition, two streptokinase-specific T cell clones recognized only the intact molecule and none of the molecular fragments. These two clones probably recognized an antigenic epitope including one of the methionine residues used for molecular cleavage. We conclude that T cell proliferative responses to streptokinase are determined by recognition of at least five different antigenic epitopes distributed along the entire streptokinase polypeptide chain.

Adult↗

PubMed1984

Streptokinase thrombolysis in experimental coronary artery thrombosis: pattern of reflow and effect of a stenosis.

We studied recanalization of an obstructed left circumflex coronary artery by streptokinase in open-chest anesthetized dogs. Thrombotic occlusion was induced by a 100 microA anodal current selectively delivered to the intimal surface of the vessel. Intracoronary streptokinase (50,000 U) or saline was infused over a 50-min period beginning at either 30 min or 90 min after occlusion. Continuous recordings were made of antegrade circumflex flow and regional myocardial function, which was quantitated using sonomicrometer crystals in the regions of the left anterior descending and circumflex coronary arteries. In some experiments a fixed stenosis, having no effect on mean circumflex coronary artery blood flow, was placed at the site of subsequent thrombus formation. The presence of a stenosis decreased the weight of occlusive thrombi obtained from nonreperfused saline controls by 40% and increased the proportion of animals successfully reperfused by streptokinase from 13 to 76%. Streptokinase reduced thrombus mass by 44% in animals recanalized in the presence of the stenosis. On the average, reflow was established after 26 min of streptokinase infusion, was less in magnitude than pre-occlusion flow, and was unstable and intermittent, being marked by frequent reocclusions. Initiating treatment at 30 min or 90 min post-occlusion did not influence characteristics of the reflow. Return of myocardial contractility in the ischemic bed was not detected during the immediate reperfusion period in the majority of these experiments.

Animals↗

PubMed1989

Streptokinase improves reperfusion blood flow after coronary artery occlusion.

Streptokinase is an effective thrombolytic agent which, with early restoration of coronary blood flow, has the potential for limiting infarct size. Distinct from thrombolysis, we studied the effects of streptokinase on reperfusion coronary blood flow and infarct size. Open-chest anesthetized canines underwent a 90 minute snare occlusion of the left circumflex coronary artery followed by release and reperfusion through a critical stenosis for 6 hours. The animals were assigned randomly to two groups. Intracoronary streptokinase [group 1 (n = 8): 6000 IU/kg in 3 ml of saline] or saline [group 2 (n = 8): 3 ml of saline] was infused at 0.05 ml/min for 60 minutes beginning 30 minutes before reperfusion. Coronary blood flow was stable in group 1 during reperfusion, while in group 2 it fell during 6 hours of reperfusion (30 +/- 4 ml/min to 18 +/- 2 ml/min, P = 0.05). The ST-segment elevation on the limb lead II electrocardiogram 15 minutes after coronary artery occlusion was similar in both groups (group 1: 3.9 +/- 0.6 mV, group 2: 2.3 +/- 0.5 mV), suggesting the extent of myocardial ischemia was also similar in both groups. The infarct sizes were similar when expressed both as a percent of the total left ventricular mass [(IZ/LV) group 1: 17 +/- 2.5%, group 2: 17.5 +/- 2.5%] or as a percent of the area at risk of infarction [(IZ/AR) group 1: 39 +/- 6%, group 2: 39 +/- 5%]. In both groups, the mass of left ventricle dependent on the blood flow distribution of the left circumflex coronary artery was similar when compared to total left ventricular mass [(AR/LV) group 1: 41 +/- 3%, group 2: 44 +/- 4%]. These results demonstrate that streptokinase maintains reperfusion coronary blood flow through a critical stenosis at a rate similar to baseline levels. Despite the fact that coronary blood flow remained stable with streptokinase during reperfusion, infarct size was not limited after 90 minutes of fixed coronary artery occlusion in this canine model of myocardial injury.

Animals↗

PubMed1990

Effect of intravenous streptokinase on the relation between initial ST-predicted size and final QRS-estimated size of acute myocardial infarcts.

Thrombolytic therapy has been documented to reduce acute myocardial infarct size. The previously established relation between initial ST segment elevation and final electrocardiographic (ECG) myocardial infarct size in patients without coronary reperfusion might therefore be altered by thrombolytic therapy. The effect of intravenous streptokinase on this relation was therefore studied in 73 patients with initial acute myocardial infarction who had participated in the Second International Study of Infarct Survival (ISIS-2). Patients who received streptokinase were considered as one group and patients who did not receive streptokinase as a control group. Final myocardial infarct size, which was estimated from the QRS score, was predicted from the admission standard ECG by previously developed formulas based on ST segment elevation. In the 40 control patients there was no change from ST-predicted to final QRS-estimated infarct size (median 17.7% versus 18.3%; p = NS). In the 33 patients in the streptokinase group, there was a highly significant decrease from predicted to final myocardial infarct size (median 21.9% versus 16.2%; p less than 0.0002). This decrease was found for both anterior (median 23.7% versus 19.5%; p less than 0.03) and inferior (median 21.9% versus 12.0%; p = 0.001) infarct locations. Multiple regression analysis adjusting for differences in predicted infarct size confirmed the significance of streptokinase on the difference in infarct size (p = 0.006). Based on the variability of the percent change from predicted to final infarct size in the control group, a threshold decrease greater than or equal to 20% is required for identification of salvage.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspirin↗

PubMed1992

Confronting the issues of patient safety and investigator conflict of interest in an international clinical trial of myocardial reperfusion. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) Steering Committee.

The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial is a large scale international trial of new myocardial reperfusion strategies. The primary hypothesis is that early and sustained coronary artery recanalization will be associated with a significant reduction in mortality. The four regimens that are being tested are 1) streptokinase with subcutaneous heparin; 2) streptokinase with intravenous heparin; 3) accelerated recombinant tissue-type plasminogen activator (rt-PA) with intravenous heparin; and 4) combination streptokinase, rt-PA and intravenous heparin. The planned recruitment of 41,600 patients in 1,500 sites from 15 countries is expected to be completed by December 1992 and will enable detection of a 15% reduction or 1% absolute difference in mortality compared with that associated with standard therapy (streptokinase and subcutaneous heparin). In designing the trial, two important issues were directly addressed. First, a strategy was developed to provide assurance of patient safety during large scale investigational use of an aggressive thrombolytic regimen. This includes fascimile transmission of a one-page safety summary form to the Data Coordinating Center within 24 h of death or discharge, acceptance of the concept of "net clinical benefit" and close surveillance of the trial's progress by the independent Data and Safety Monitoring Committee. Second, to avoid potential conflict of interest beyond elimination of any position of financial equity, the Steering Committee unanimously voted to prohibit any honoraria for speaking engagements, payment for consultancy or travel or reimbursement of any kind from any of the five corporate sponsors until 1 year after publication of the results. Incorporation of these approaches may facilitate the design of future large scale randomized trials in cardiovascular medicine.

Biomedical Research↗

PubMed1993

Combined thromboxane A2 synthase inhibition and prostaglandin endoperoxide receptor antagonism limits myocardial infarct size after mechanical coronary occlusion and reperfusion at doses enhancing coronary thrombolysis by streptokinase.

OBJECTIVES: We sought to examine to what extent a combination of strong thromboxane A2 synthase inhibition and moderate endoperoxide receptor blockade enhances streptokinase-induced coronary thrombolysis and provides anti-ischemic activity independent from its thrombolytic activity. METHODS: Coronary thrombi, induced by crush injury and stenosis of the coronary artery, were lysed with streptokinase, 10,000 IU/kg body weight over 90 min, in anesthetized dogs receiving solvent (n = 11), ridogrel, 0.31 mg/kg intravenously, for thromboxane A2 synthase inhibition (n = 7) or ridogrel, 5 mg/kg, for additional prostaglandin endoperoxide receptor antagonism in addition to thromboxane A2 synthase inhibition (n = 7) 10 min before the administration of streptokinase. RESULTS: Thrombolytic efficacy was greatest in animals receiving both dual-acting ridogrel, 5 mg/kg intravenously, and streptokinase as evidenced by the highest incidence of high grade coronary reperfusion (solvent 3 of 11; ridogrel, 0.31 mg/kg, 5 of 7; ridogrel, 5 mg/kg, 7 of 7; p < 0.05 vs. solvent) within the shortest delay (solvent 210 min; ridogrel, 0.31 mg/kg, 85 min; ridogrel, 5 mg/kg, 37 min; p < 0.05 vs. solvent and ridogrel, 0.31 mg/kg) and the lowest incidence of reocclusion (solvent 5 of 7; ridogrel, 0.31 mg/kg, 2 of 7; ridogrel, 5 mg/kg, 1 of 7; p < 0.05 versus solvent). Myocardial infarct size after coronary artery ligation (90 min) and subsequent reperfusion (150 min) in anesthetized dogs was 49.3 +/- 4.3% versus 29 +/- 3.9% (p < 0.05 vs. solvent) of the area of the left ventricle at risk in dogs receiving solvent (n = 9) or ridogrel, 5 mg/kg intravenously (n = 10), respectively, despite similar hemodynamic characteristics, collateral blood flow and area at risk in both groups. CONCLUSIONS: Combined thromboxane A2 synthase inhibition and endoperoxide receptor antagonism 1) upgrades thrombolysis with streptokinase in canine coronary arteries, 2) limits myocardial infarct size after nonthrombotic coronary occlusion and reperfusion, and 3) may preserve ventricular function compromised by coronary occlusion through dual manipulation of the arachidonic acid cascade in blood and myocardial tissue, respectively.

Animals↗

PubMed1995

Contemporary reperfusion therapy for cardiogenic shock: the GUSTO-I trial experience. The GUSTO-I Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.

OBJECTIVES: This study sought to examine the incidence, temporal profile and clinical implications of shock in a large trial of thrombolytic therapy for acute myocardial infarction. BACKGROUND: Despite advances in the treatment of acute ischemic syndromes, cardiogenic shock remains associated with significant morbidity and mortality. METHODS: Patients who presented within 6 h of symptom onset were randomized to four treatment strategies: 1) streptokinase plus subcutaneous heparin; 2) streptokinase plus intravenous heparin; 3) accelerated recombinant tissue-type plasminogen activator (rt-PA) plus intravenous heparin; or 4) streptokinase and rt-PA plus intravenous heparin. The primary end point was 30-day all-cause mortality. RESULTS: Shock occurred in 2,972 patients (7.2%): 315 (11%) had shock on arrival, and 2,657 (89%) developed shock after hospital admission. Reinfarction occurred in 11% of patients who developed shock compared with 3% of patients without shock. The mortality rate was significantly higher in patients who presented with (57%) or developed (55%) shock than in those without shock (3%) (p < 0.001). Shock developed significantly less frequently in patients receiving rt-PA. There were fewer deaths in patients who presented with shock and were treated with streptokinase plus intravenous heparin or who developed shock and were treated with streptokinase plus subcutaneous heparin. Patients who developed shock had a significantly lower 30-day mortality rate if angioplasty was performed. CONCLUSIONS: Because cardiogenic shock occurred most often after admission and with recurrent ischemia and reinfarction, recognizing signs of incipient shock may improve outcome. Fewer patients treated with rt-PA developed shock, yet those developing shock had the same high mortality rate as those presenting with shock, regardless of treatment. Only angioplasty was associated with a significantly lower mortality rate.

Aged↗

PubMed1998

Pretreatment plasminogen activator inhibitor-1 (PAI-1) levels and the outcome of thrombolysis with streptokinase in patients with acute myocardial infarction.

BACKGROUND: The risk for reinfarctions and delays in reperfusion after streptokinase therapy may be caused by the antifibrinolytic effect of platelet-derived type 1 plasminogen activator inhibitor (PAI-1). This study aims to show the relation of pretreatment PAI-1 levels of patients with acute myocardial infarction treated with streptokinase therapy and the outcome of fibrinolysis, with the emphasis on reperfusion and reinfarction. METHODS: Pretreatment PAI-1 levels of 60 patients with acute myocardial infarction, treated with streptokinase, were determined by the chromogenic method. Failure of thrombolysis with streptokinase was present when reperfusion was delayed as assessed by noninvasive reperfusion criteria, or reinfarctions developed. RESULTS: Mean pretreatment PAI-1 level of patients was 6.3+/-1.2 U/ml; span 1.2 U/ml to 34.0 U/ml. Thrombolysis with streptokinse failed significantly in patients with pretreatment PAI-1 levels >4.0 U/ml (p < 0.05), mainly because of significant occurrence of reinfarction (p < 0.05), but less to delayed reperfusion (p > 0.05). CONCLUSION: Failure of thrombolysis with streptokinase is significantly associated with pretreatment PAI-1 levels of >4.0 U/ml.

Aged↗

PubMed1999

Thrombolysis with saruplase versus streptokinase in acute myocardial infarction: five-year results of the PRIMI trial.

BACKGROUND: Short-term safety and efficacy of thrombolysis with saruplase in acute myocardial infarction have been shown in several trials. To assess long-term outcome of patients treated with saruplase or streptokinase for myocardial infarction, a 5-year follow-up of patients included in the Pro-Urokinase in Myocardial Infarction Trial was performed. METHODS AND RESULTS: Follow-up data are available from 8 centers on 255 (92.4%) of 276 included patients. The 5-year mortality rate was comparable with 20.8% of patients in the saruplase group and 16.9% in the streptokinase group (odds ratio 1.29, 95% confidence interval 0.69 to 2.42). In both groups, a considerable number of fatal cardiovascular events occurred more than 1 year after study inclusion. Rates of percutaneous transluminal coronary angioplasty and coronary artery bypass grafting were comparable in both groups. Reinfarction within 5 years occurred in 19.0% of patients in the saruplase group and tended to be less frequent at 10.8% after streptokinase treatment (odds ratio 1.94, 95% confidence interval 0.98 to 3.84). In both groups, the majority of reinfarctions took place more than 3 months after study inclusion. The 5-year stroke rate was 3.6% and 7.2% in the saruplase and streptokinase groups, respectively (odds ratio 0.49, 95% confidence interval 0.16 to 1.47). Subjective symptoms of heart failure and angina pectoris were comparable in both groups. CONCLUSIONS: Our data are consistent with a similar long-term outcome for patients treated with saruplase or streptokinase. Despite the low-risk profile of the patient cohort, there were considerable adverse event rates over a 5-year period.

Aged↗

PubMed2000

Asp41-His48 region of streptokinase is important in binding to a substrate plasminogen.

Streptokinase is a plasminogen activator protein produced by several strains of beta-hemolytic streptococci. Random mutagenesis of streptokinase was carried out for the determination of critical amino acid residues in plasminogen activation. We selected and sequenced 14 streptokinase mutants with no plasminogen activation activity on skim milk-plasminogen overlay plate. Specific activities of the selected streptokinase mutants were determined with chromogenic assay. Eight mutants (V19F, V35E, E85D, L292R, D325P, D341E, I345N, and M369L) resulted in greatly decreased amidolytic activities. However, unexpectedly, six mutants (D41C, S44K, S44P, R45P, H48T, and D220G) showed substantial amidolytic activities comparable to that of wild type. Moreover, five-point mutations were concentrated on the Asp41-His48 region. These data indicate that the Asp41-His48 region in a streptokinase-plasminogen binary complex plays an important role in binding to a substrate plasminogen.

Amidohydrolases↗