First Structural Model of Full-Length Human Tissue-Plasminogen Activator: A SAXS Data-Based Modeling Study.

Rathore, Yogendra S and Rehan, Mohammad and Pandey, Kalpana and Sahni, Girish and Ganguly, Ashish (2012) First Structural Model of Full-Length Human Tissue-Plasminogen Activator: A SAXS Data-Based Modeling Study. The journal of physical chemistry. B, 116 (1). pp. 496-502. ISSN 1520-5207

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Abstract

Human tissue-plasminogen activator (t-PA) is a multidomain glycoprotein which holds high biomedical value due to its therapeutic role in clot-specific fibrinolysis. Although atomic-resolution structures of individual domains except Kringle1 are available, no structural information is available on how these domains and glycosylation are oriented in space relative to each other in the full-length protein. SAXS intensity profile acquired from samples of t-PA was used to "steer" structures of individual domains and the homology model of the first kringle domain to generate a structural model of the protein part of t-PA. Differences in the shape profiles of SAXS data-based dummy atom and proteinogenic models aided in grafting glycosylated moieties on the coordinates of t-PA. According to previously reported mutagenesis-rendered altered functional profiles, normal-mode analysis of our model revealed that the fibrin binding F/E domains "communicate" with the active-site in the P domain via Kringle2, while Kringle1 is positioned away from these long-distance interactions.

Item Type:	Article
Additional Information:	Copyright of this article belongs to ACS.
Subjects:	Q Science > QR Microbiology
Depositing User:	Dr. K.P.S.Sengar
Date Deposited:	27 Jan 2012 15:32
Last Modified:	22 Jul 2015 03:52
URI:	http://crdd.osdd.net/open/id/eprint/691

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