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Asn12 and Asn278 : Critical Residues for In Vitro Biological Activity of Reteplase
Joint Authors
Sundaram, Kalyana R.
Padmanabhan, Sriram
Tandra, Sunil K.
Mandi, Naganath
Bandyopadhyay, Suman
Source
Issue
Vol. 2010, Issue 2010 (31 Dec. 2010), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2010-06-21
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Abstract EN
Reteplase (rPA) is a thrombolytic agent used for the treatment of acute myocardial infarction.
We studied the expression of rPA and its selected asparagine mutants after integration into the Pichia genome.
Though methanol induction of the native and the rPA mutants showed similar expression levels (~200–250 mg/L), the mutants displayed significant loss of protease activity.
Strikingly, the clot lysis activities of these mutants were considerably different.
While mutation of Asn12 (N12P) of the Kringle 2 domain showed delayed clot lysis activity (t1/2=38 min) compared to the native rPA (t1/2=33 min), a faster rate of clot lysis (t1/2=27 min) was observed when the Asn278 (N278S) of the serine protease domain was mutated.
Interestingly, the slowest clot lysis activity (t1/2=49 min) demonstrated by the double mutant (N12P, N278S) suggests the dominant role of Asn12 in regulating the fibrinolytic activity of rPA.
The results presented in this paper indicate that the fibrinolytic and the proteolytic activities of rPA are independent of each other.
American Psychological Association (APA)
Mandi, Naganath& Sundaram, Kalyana R.& Tandra, Sunil K.& Bandyopadhyay, Suman& Padmanabhan, Sriram. 2010. Asn12 and Asn278 : Critical Residues for In Vitro Biological Activity of Reteplase. Advances in Hematology،Vol. 2010, no. 2010, pp.1-9.
https://search.emarefa.net/detail/BIM-451656
Modern Language Association (MLA)
Mandi, Naganath…[et al.]. Asn12 and Asn278 : Critical Residues for In Vitro Biological Activity of Reteplase. Advances in Hematology No. 2010 (2010), pp.1-9.
https://search.emarefa.net/detail/BIM-451656
American Medical Association (AMA)
Mandi, Naganath& Sundaram, Kalyana R.& Tandra, Sunil K.& Bandyopadhyay, Suman& Padmanabhan, Sriram. Asn12 and Asn278 : Critical Residues for In Vitro Biological Activity of Reteplase. Advances in Hematology. 2010. Vol. 2010, no. 2010, pp.1-9.
https://search.emarefa.net/detail/BIM-451656
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-451656