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1. PARP inhibitor predictive value of the Leuven HRD test compared with Myriad MyChoice CDx PLUS HRD on 468 ovarian cancer patients from the PAOLA-1/ENGOT-ov25 trial

Author

Loverix L., Vergote I., Busschaert P., Vanderstichele A., Venken T., Boeckx B., Harter P., Brems H., Van Nieuwenhuysen E., Pignata S., Baert T., Gonzalez-Martin A., Han S., Marth C., Neven P., Colombo N., Berteloot P., Mäenpää J., Olbrecht S., Laga T., Sablon E., Ray-Coquard I., Pujade-Lauraine E., Lambrechts D., Van Gorp T., Loverix, L, Vergote, I, Busschaert, P, Vanderstichele, A, Venken, T, Boeckx, B, Harter, P, Brems, H, Van Nieuwenhuysen, E, Pignata, S, Baert, T, Gonzalez-Martin, A, Han, S, Marth, C, Neven, P, Colombo, N, Berteloot, P, Mäenpää, J, Olbrecht, S, Laga, T, Sablon, E, Ray-Coquard, I, Pujade-Lauraine, E, Lambrechts, D, and Van Gorp, T

Subjects
Targeted therapy, Cancer Research, PARP inhibitor, Oncology, Ovarian cancer, HRD testing, Leuven HRD test
Abstract

Background: The PAOLA-1/ENGOT-ov25 trial showed improved progression-free (PFS) and overall survival (OS) in homologous recombination deficient (HRD) positive patients treated with olaparib, but not when HRD negative (HRD tested with MyChoice CDx PLUS [Myriad test]). Patients and methods: The academic Leuven HRD test consists of capture-based targeted sequencing of genome-wide single-nucleotide polymorphisms and coding exons of eight HR genes including BRCA1, BRCA2, and TP53. We compared the predictive value of the Leuven HRD versus Myriad HRD test for PFS and OS in the randomised PAOLA-1 trial. Results: 468 patients had left-over DNA after Myriad testing for Leuven HRD testing. Positive/negative/overall percent agreement for the Leuven versus Myriad HRD status was 95%/86%/91%, respectively. Tumours were HRD+ in 55% and 52%, respectively. In Leuven HRD+ patients, 5 years PFS (5yPFS) was 48.6% versus 20.3% (HR 0.431; 95% confidence intervals (CI) 0.312–0.595) for olaparib versus placebo, respectively (Myriad test 0.409; 95% CI 0.292–0.572). In Leuven HRD+/BRCAwt patients 5yPFS was 41.3% versus 12.6% (HR 0.497; 95% CI 0.316–0.783), and 43.6% versus 13.3% (HR 0.435; 95% CI 0.261–0.727) for the Myriad test. 5yOS was prolonged in the HRD+ subgroup with both tests 67.2% versus 54.4% (HR 0.663; 95% CI 0.442–0.995) for the Leuven test, and 68.0% versus 51.8% (HR 0.596 95% CI 0.393–0.904) for the Myriad test. HRD status was undetermined in 10.7% and 9.4% of the samples, respectively. Conclusions: A robust correlation between the Leuven HRD and Myriad test was observed. For HRD+ tumours, the academic Leuven HRD showed a similar difference in PFS and OS as the Myriad test.

Published
2023
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2. PARP inhibitor predictive value of the Leuven HRD test compared with Myriad MyChoice CDx PLUS HRD on 468 ovarian cancer patients from the PAOLA-1/ENGOT-ov25 trial

Author

Loverix, L, Vergote, I, Busschaert, P, Vanderstichele, A, Venken, T, Boeckx, B, Harter, P, Brems, H, Van Nieuwenhuysen, E, Pignata, S, Baert, T, Gonzalez-Martin, A, Han, S, Marth, C, Neven, P, Colombo, N, Berteloot, P, Mäenpää, J, Olbrecht, S, Laga, T, Sablon, E, Ray-Coquard, I, Pujade-Lauraine, E, Lambrechts, D, Van Gorp, T, Loverix L., Vergote I., Busschaert P., Vanderstichele A., Venken T., Boeckx B., Harter P., Brems H., Van Nieuwenhuysen E., Pignata S., Baert T., Gonzalez-Martin A., Han S., Marth C., Neven P., Colombo N., Berteloot P., Mäenpää J., Olbrecht S., Laga T., Sablon E., Ray-Coquard I., Pujade-Lauraine E., Lambrechts D., Van Gorp T., Loverix, L, Vergote, I, Busschaert, P, Vanderstichele, A, Venken, T, Boeckx, B, Harter, P, Brems, H, Van Nieuwenhuysen, E, Pignata, S, Baert, T, Gonzalez-Martin, A, Han, S, Marth, C, Neven, P, Colombo, N, Berteloot, P, Mäenpää, J, Olbrecht, S, Laga, T, Sablon, E, Ray-Coquard, I, Pujade-Lauraine, E, Lambrechts, D, Van Gorp, T, Loverix L., Vergote I., Busschaert P., Vanderstichele A., Venken T., Boeckx B., Harter P., Brems H., Van Nieuwenhuysen E., Pignata S., Baert T., Gonzalez-Martin A., Han S., Marth C., Neven P., Colombo N., Berteloot P., Mäenpää J., Olbrecht S., Laga T., Sablon E., Ray-Coquard I., Pujade-Lauraine E., Lambrechts D., and Van Gorp T.

Abstract

Background: The PAOLA-1/ENGOT-ov25 trial showed improved progression-free (PFS) and overall survival (OS) in homologous recombination deficient (HRD) positive patients treated with olaparib, but not when HRD negative (HRD tested with MyChoice CDx PLUS [Myriad test]). Patients and methods: The academic Leuven HRD test consists of capture-based targeted sequencing of genome-wide single-nucleotide polymorphisms and coding exons of eight HR genes including BRCA1, BRCA2, and TP53. We compared the predictive value of the Leuven HRD versus Myriad HRD test for PFS and OS in the randomised PAOLA-1 trial. Results: 468 patients had left-over DNA after Myriad testing for Leuven HRD testing. Positive/negative/overall percent agreement for the Leuven versus Myriad HRD status was 95%/86%/91%, respectively. Tumours were HRD+ in 55% and 52%, respectively. In Leuven HRD+ patients, 5 years PFS (5yPFS) was 48.6% versus 20.3% (HR 0.431; 95% confidence intervals (CI) 0.312–0.595) for olaparib versus placebo, respectively (Myriad test 0.409; 95% CI 0.292–0.572). In Leuven HRD+/BRCAwt patients 5yPFS was 41.3% versus 12.6% (HR 0.497; 95% CI 0.316–0.783), and 43.6% versus 13.3% (HR 0.435; 95% CI 0.261–0.727) for the Myriad test. 5yOS was prolonged in the HRD+ subgroup with both tests 67.2% versus 54.4% (HR 0.663; 95% CI 0.442–0.995) for the Leuven test, and 68.0% versus 51.8% (HR 0.596 95% CI 0.393–0.904) for the Myriad test. HRD status was undetermined in 10.7% and 9.4% of the samples, respectively. Conclusions: A robust correlation between the Leuven HRD and Myriad test was observed. For HRD+ tumours, the academic Leuven HRD showed a similar difference in PFS and OS as the Myriad test.

Published
2023

4. Antimicrobial Peptides of Lactic Acid Bacteria: Mode of Action, Genetics and Biosynthesis

Author

Sablon, E., Contreras, B., Vandamme, E., Scheper, T., editor, Babel, W., editor, Blanch, H. W., editor, Cooney, C. L., editor, Endo, I., editor, Enfors, S. -O., editor, Eriksson, K. -E. L., editor, Fiechter, A., editor, Hoare, M., editor, Mattiasson, B., editor, Rehm, H. J., editor, Rogers, P. L., editor, Sahm, H., editor, Schügerl, K., editor, Stephanopoulos, G., editor, Tsao, G. T., editor, Venkat, K., editor, Villadsen, J., editor, von Stockar, U., editor, and Wandrey, C., editor

Published
2000
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6. Evaluation of a novel subtilisin inhibitor gene and mutant derivatives for the expresion and secretion of mouse tumor necrosis factor alpha by Streptomyces lividans

Author

Lammertyn, E., Mellaert, L. van, Schacht, S., Dillen, C., Sablon, E., Broekhoven, A. van, and Anne, J.

Subjects
Tumor necrosis factor -- Genetic aspects, Microbial genetics -- Research, Streptomyces -- Genetic aspects, Bacterial proteins -- Genetic aspects, Biological sciences
Abstract

The complementary DNA of the murine tumor necrosis factor (mTNF) was fused with the signal sequence of the gene encoding novel subtilisin inhibitor (VSI) of Streptomyces venezuelae. Immunoblot analysis of the recombinant mTNF produced by S. lividans transformants with mutated VSI signal peptides indicated the presence of varied levels of mTNF secretion that was altered by the effect of positive charges in the N regions on the signal peptides. However, the presence of positive charges in the N region was not an integral component of protein export.

Published
1997

7. Isolation, purification, and amino acid sequence of lactobin A, one of the two bacteriocins produced by Lactobacillus amylovorus LMG P-13139

Author

Contreras, B.G.L., Vuyst, L. de, Devreese, B., Busanyova, K., Raymaeckers, J., Bosman, F., Sablon, E., and Vandamme, E.J.

Subjects
Amino acid sequence -- Analysis, Lactobacillus -- Research, Bacterial proteins -- Research, Biological sciences
Abstract

Lactobacillus amylovorus LMG P-13139 produces a 4.5 kDa bacteriocin, lactobin A, that is a heat stable, non-lanthionine-containing membrane-active peptide. It belongs to the class IIb bacteriocins. The peptide's N-terminal contains 50 amino acids. The bacteriocin consists of 26% glycine residues and 40% hydrophobic residues. It shows structural homology with the lafX gene product. A hydrophobic membrane-integrated stretch extends from residues 24 to 45, and the extreme N- and C-terminals of lactobin A have a hydrophilic nature.

Published
1997

14. Clinical impact of circulating tumor RAS and BRAF mutation dynamics in metastatic colorectal cancer patients treated with first-line chemotherapy plus anti-EGFR therapy: Combined analysis of two prospective clinical trials

Author

Montagut, C., primary, Alonso, V., additional, Escudero, P., additional, Fernández-Martos, C., additional, Salud Salvia, A., additional, Méndez, M., additional, Gallego Plazas, J., additional, Rodriguez, J.R., additional, Martín-Richard, M., additional, Fernández-Plana, J., additional, Aparicio, J., additional, Feliu Batlle, J., additional, García de Albéniz, X., additional, Rojo, F., additional, Fernández, V., additional, Claes, B., additional, Maertens, G.G., additional, Sablon, E., additional, Jacobs, B.A.W., additional, and Maurel, J., additional

Published
2018
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15. Detection of microsatellite instability (MSI) with a novel set of 7 Idylla biomarkers on colorectal cancer samples in a multi-center study

Author

De Craene, B., primary, Van de Velde, J., additional, Bellon, E., additional, Gazin, M., additional, Rondelez, E., additional, Vandenbroeck, L., additional, Vanhoey, T., additional, Elsen, N., additional, Melchior, L.C., additional, Willemoe, G.L., additional, Watkin, E., additional, Arens, N., additional, Altmann, C., additional, Decanniere, K., additional, Sablon, E., additional, and Maertens, G.G., additional

Published
2018
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18. Hepatitis virus and HIV infections in inmates of a state correctional facility in Mexico

Author

Cosme Alvarado-Esquivel, Sablon E, Sergio Estrada-Martínez, and Sergio Arturo Martínez-García

Subjects
Male, HBsAg, Epidemiology, Population, Comorbidity, Risk Assessment, Cohort Studies, Acquired immunodeficiency syndrome (AIDS), Confidence Intervals, Odds Ratio, Prevalence, medicine, Humans, Hepatitis Antibodies, Sida, education, Mexico, Hepatitis, education.field_of_study, AIDS-Related Opportunistic Infections, biology, business.industry, Prisoners, virus diseases, Hepatitis A, Hepatitis B, medicine.disease, biology.organism_classification, Hepatitis C, Virology, Hepatitis D, digestive system diseases, Cross-Sectional Studies, Infectious Diseases, Prisons, DNA, Viral, Immunology, biology.protein, Female, Viral disease, Antibody, business, Research Article
Abstract

SUMMARY We sought to determine the prevalence and associated characteristics of hepatitis A, B, C and D viruses and HIV infections in a prison in Durango, Mexico. Sera from 181 inmates were analysed for HAV antibody, hepatitis B core antibody (HBcAb), hepatitis B surface antigen (HBsAg), HCV antibody, HDV antibody, HIV antibody and HCV genotypes. Prevalence of HAV antibody, HBcAb, HBsAg, HCV antibody, HDV antibody and HIV antibody were 99-4, 4-4, 0-0, 10 0, 0-0 and 0-6% respectively. HCV genotype la predominated in HCV-infected inmates (62-5 %), followed by HCV genotype lb (25 %) and HCV genotype 3 (12-5 %). An association between HBV infection and age > 30 years was found. HCV infection was associated with being born in Durango City, history of hepatitis, ear piercing, tattooing, drug abuse history, intravenous drug use and lack of condom use. We concluded that the prevalence of HAV, HBV, HDV and HIV infections in inmates in Durango, Mexico were comparable to those of the Mexican general population and blood donors, but lower than those reported in other prisons around the world. However, HCV infection in inmates was higher than that reported in Mexican blood donors but lower than those reported in other prisons of the world. These results have implications for the optimal planning of preventive and therapeutic measures.

Published
2005
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20. Ultra-rapid, sensitive, and fully automated extended RAS testing for metastatic colorectal cancer – evaluation of an NRAS/BRAF/EGFR492 module

Author

Vercauteren, E., primary, Bellon, E., additional, Vermeiren, K., additional, De Freitas, F., additional, De Haes, E., additional, Van Gestel, S., additional, Murray, S., additional, Grauslund, M., additional, Melchior, L., additional, D'Haene, N., additional, Le Mercier, M., additional, Bellosillo, B., additional, Montagut, C., additional, Van Brussel, M., additional, Sablon, E., additional, and Maertens, G., additional

Published
2016
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22. 545P - Clinical impact of circulating tumor RAS and BRAF mutation dynamics in metastatic colorectal cancer patients treated with first-line chemotherapy plus anti-EGFR therapy: Combined analysis of two prospective clinical trials

Author

Montagut, C., Alonso, V., Escudero, P., Fernández-Martos, C., Salud Salvia, A., Méndez, M., Gallego Plazas, J., Rodriguez, J.R., Martín-Richard, M., Fernández-Plana, J., Aparicio, J., Feliu Batlle, J., García de Albéniz, X., Rojo, F., Fernández, V., Claes, B., Maertens, G.G., Sablon, E., Jacobs, B.A.W., and Maurel, J.

Published
2018
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27. The emergence of YMDD mutants precedes biochemical flare by 19 weeks in lamivudine-treated chronic hepatitis B patients: an opportunity for therapy reevaluation

Author

França,P.H.C., Coelho,H.S.M., Brandão,C.E., Segadas,J.A., Quintaes,R.F., Carrilho,F.J., Ono-Nita,S., Mattos,A.A., Tovo,C., Gouvea,V.S., Sablon,E., and Vanderborght,B.O.M.

Subjects
lcsh:R5-920, Hepatitis B virus, lcsh:Biology (General), Lamivudine, Drug resistance, Antiviral therapy, lcsh:Medicine (General), Hepatitis B, lcsh:QH301-705.5, YMDD variants
Abstract

Given the loss of therapeutic efficacy associated with the development of resistance to lamivudine (LMV) and the availability of new alternative treatments for chronic hepatitis B patients, early detection of viral genotypic resistance could allow the clinician to consider therapy modification before viral breakthrough and biochemical relapse occur. To this end, 28 LMV-treated patients (44 ± 12 years; 24 men), on their first therapy schedule, were monitored monthly at four Brazilian centers for the emergence of drug resistance using the reverse hybridization-based INNO-LiPA HBV DR assay and occasionally sequencing (two cases). Positive viral responses (HBV DNA clearance) after 6, 12, and 18 months of therapy were achieved by 57, 68, and 53% of patients, while biochemical responses (serum alanine aminotransferase normalization) were observed in 82, 82, and 53% of cases. All viral breakthrough cases (N = 8) were related to the emergence of YMDD variants observed in 7, 21, and 35% of patients at 6, 12, and 18 months, respectively. The emergence of these variants was not associated with viral genotype, HBeAg expression status, or pretreatment serum alanine aminotransferase levels. The detection of resistance-associated mutations was observed before the corresponding biochemical flare (41 ± 14 and 60 ± 15 weeks) in the same individuals. Then, if highly sensitive LMV drug resistance testing is carried out at frequent and regular intervals, the relatively long period (19 ± 2 weeks) between the emergence of viral resistance and the onset of biochemical relapse can provide clinicians with ample time to re-evaluate drug therapy.

Published
2007

28. 169 BRAF mutation testing in cell-free DNA from plasma of patients with advanced cancers using a novel, rapid, automated molecular diagnostics prototype platform (Idylla™)

Author

Janku, F., primary, Huang, H.J., additional, Claes, B., additional, Falchook, G.S., additional, Naing, A., additional, Piha-Paul, S., additional, Tsimberidou, A.M., additional, Zinner, R.G., additional, Karp, D.D., additional, Fu, S., additional, Subbiah, V., additional, Hong, D.S., additional, Wheler, J.J., additional, Luthra, R.G., additional, Patel, S.P., additional, Kopetz, E.S., additional, Sablon, E., additional, Maertens, G., additional, Kurzrock, R., additional, and Meric-Bernstam, F., additional

Published
2014
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31. Validation of the INNO-LiPA HBV DR assay (version 2) in monitoring hepatitis B virus-infected patients receiving nucleoside analog treatment

Author

Niesters, H.G.M. (Bert), Zoulim, F. (Fabien), Pichoud, C. (Christian), Buti, M. (Miquel), Shapiro, F., D'Heuvaert, N., Celis, L. (Linda), Doutreloigne, J. (Joke), Sablon, E. (Erwin), Niesters, H.G.M. (Bert), Zoulim, F. (Fabien), Pichoud, C. (Christian), Buti, M. (Miquel), Shapiro, F., D'Heuvaert, N., Celis, L. (Linda), Doutreloigne, J. (Joke), and Sablon, E. (Erwin)

Abstract

Hepatitis B virus (HBV) antiviral drug resistance mutations prevent successful outcome of treatment and lead to worsening of liver disease. Detection of its emergence permits opportune treatment with alternative drugs. Unfortunately, the use of newly approved antivirals, including adefovir dipivoxil, emtricitabine, and telbivudine, is also associated with the development of drug resistance, albeit to a lesser extent than the use of lamivudine. The objectives of this work were to assess the performance characteristics (sensitivity and accuracy) of an updated drug resistance test, the INNO-LiPA HBV DR v2, which includes detection of mutations associated with lamivudine, adefovir, emtricitabine, and telbivudine resistance, and to compare the results with consensus sequencing of serum samples from patients treated with HBV antivirals. Diagnostic sensitivity, defined as detection of a positive amplification line on the line probe assay (LiPA) strip, was 94.8% (95% confidence interval [CI], 89.7 to 97.9) after initial testing, increasing to 96.3% (95% CI, 91.6 to 98.8) after repeat test 1 and to 100% (95% CI, 97.3 to 100.0) after repeat test 2. In diagnostic accuracy determinations, full concordance was observed between sequencing and LiPA for 77.0% of the codons tested (620/805 codons [95% CI, 74.0 to 79.9]), whereas LiPA and sequencing were partially concordant 22% of the time (177/805 codons). In 167 out of 177 cases, LiPA detected a wild-type/mutant mixture whereas sequencing detected only one of the two results. Performance testing of the new LiPA test, the INNO-LiPA HBV DR v2, showed convincing diagnostic sensitivity and accuracy. The ability of the test to detect mixed infections and minority viral populations associated with resistance to the current generation of antivirals, including adefovir, emtricitabine, and telbivudine, makes it a useful tool for HBV therapy monitoring.

Published
2010
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32. Genotyping hepatitis C viruses from Southeast Asia by a novel line probe assay that simultaneously detects core and 5′ untranslated regions

Author

Noppornpanth, S. (Suwanna), Haagmans, B.L. (Bart), Sablon, E. (Erwin), Nys, K. (Kathy) de, Lien, T.X. (Truong Xuang), Brouwer, J. (Jan), Brussel, M. (Marianne) van, Smits, S.L. (Saskia), Poovorawan, Y. (Yong), Osterhaus, A.D.M.E. (Albert), Noppornpanth, S. (Suwanna), Haagmans, B.L. (Bart), Sablon, E. (Erwin), Nys, K. (Kathy) de, Lien, T.X. (Truong Xuang), Brouwer, J. (Jan), Brussel, M. (Marianne) van, Smits, S.L. (Saskia), Poovorawan, Y. (Yong), and Osterhaus, A.D.M.E. (Albert)

Abstract

Hepatitis C viruses (HCVs) display a high level of sequence diversity and are currently divided into six genotypes. A line probe assay (LiPA), which targets the 5′ untranslated region (5′UTR) of the HCV genome, is widely used for genotyping. However, this assay cannot distinguish many genotype 6 subtypes from genotype 1 due to high sequence similarity in the 5′UTR. We investigated the accuracy of a new generation LiPA (VERSANT HCV genotype 2.0 assay), in which genotyping is based on 5′UTR and core sequences, by testing 75 selected HCV RNA-positive sera from Southeast Asia (Vietnam and Thailand). For comparison, sera were tested on the 5′UTR based VERSANT HCV genotype assay and processed for sequence analysis of the 5′UTR-to-core and NS5b regions as well. Phylogenetic analysis of both regions revealed the presence of genotype 1, 2, 3, and 6 viruses. Using the new LiPA assay, genotypes 6c to 61 and 1a/b samples were more accurately genotyped than with the previous test only targeting the 5′UTR (96% versus 71%, respectively). These results indicate that the VERSANT HCV genotype 2.0 assay is able to discriminate genotypes 6c to 61 from genotype 1 and allows a more accurate identification of genotype 1a from 1b by using the genotype-specific core information. Copyright

Published
2006
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38. The emergence of YMDD mutants precedes biochemical flare by 19 weeks in lamivudine-treated chronic hepatitis B patients: an opportunity for therapy reevaluation

Author

França, P.H.C., primary, Coelho, H.S.M., additional, Brandão, C.E., additional, Segadas, J.A., additional, Quintaes, R.F., additional, Carrilho, F.J., additional, Ono-Nita, S., additional, Mattos, A.A., additional, Tovo, C., additional, Gouvea, V.S., additional, Sablon, E., additional, and Vanderborght, B.O.M., additional

Published
2007
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47. Generation of a mouse tumor necrosis factor mutant with antiperitonitis and desensitization activities comparable to those of the wild type but with reduced systemic toxicity

Author

Lucas, R, primary, Echtenacher, B, additional, Sablon, E, additional, Juillard, P, additional, Magez, S, additional, Lou, J, additional, Donati, Y, additional, Bosman, F, additional, Van de Voorde, A, additional, Fransen, L, additional, Männel, D N, additional, Grau, G E, additional, and de Baetselier, P, additional

Published
1997
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50. Molecular Characterization of a Novel Subtilisin Inhibitor Protein Produced by Streptomyces venezuelae CBS762.70

Author

van Mellaerp, L., Lammertyn, E., Schacht, S., Proost, P., van Damme, J., Wroblowskt, B., Anné, J., Scarcez, T., Sablon, E., Raeymaeckers, J., and van Broekhoven, A.

Abstract

We report here on the isolation and identification of a gene coding for a novel subtilisin inhibitor (VSI) isolated from Streptomyces venezuelae CBS762.70. The vsi gene was isolated on a 5-kb chromosomal Pvull fragment as identified by DNA sequencing and inhibitor activity testing of the gene product. Primer extension studies revealed that the mRNA transcriptional start point was situated at -37 and -36 relatively to the ATG start codon assuming the presence of solely one promoter. Vsi promoter strength was about double of those of ermE-Fla and aph-Pl, as tested with the mRNA production of the aphll gene preceded by the respective promoters. Translation of the vsi coding sequence revealed a 28 amino acids long signal peptide. The mature VSI protein consists of 118 amino acids of which 87% was verified by N-terminal amino acid sequence analysis. Compared with the already known Streptomyces proteinase inhibitors, VSI shows a relatively high amino acid identity in the conserved domains. Nevertheless, only a maximum amino acid identity of 56.1% was noticed and some highly conserved residues were substituted in VSI. As a consequence, VSI could be classified within a separate group of Streptomyces subtilisin inhibitors.

Published
1998
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