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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Henriksen, R.A. Articles by Usala, S.J. Search for Related Content PubMed PubMed Citation Articles by Henriksen, R.A. Articles by Usala, S.J. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Prothrombin Greenville, Arg517Gln, Identified in an Individual Heterozygous for Dysprothrombinemia R.A. Henriksen, C.K. Dunham, L.D. Miller, J.T. Casey II, J.B. Menke, C.L. Knupp, and S.J. Usala From the Section of Allergy, Asthma and Immunology, the Section of Hematology, and the Section of Endocrinology, Department of Medicine, East Carolina University, Greenville, NC. A 64-year-old white male was referred for evaluation of prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT) obtained before elective surgery with initial PT and PTT results of 14.9 and 38.4 seconds, respectively, which corrected to normal in 1:1 mixes with normal plasma. Functional prothrombin assay indicated a level of 51% with thromboplastin as an activator. The prothrombin antigen was 102%. This discordance in the functional and immunologic prothrombin levels was evidence for dysprothrombinemia. Western blotting showed that thrombin was formed at a normal rate in diluted plasma consistent with a mutation within the thrombin portion of prothrombin. DNA was isolated from leukocytes and the thrombin exons were amplified by polymerase chain reaction, cloned, and sequenced. For exon 13, eight clones were sequenced with four clones showing a point mutation in the codon for Arg517, which would result in substitution by Gln. Arg517 is part of the Arg-Gly-Asp(RGD) sequence in thrombin and contributes to an ion cluster with aspartic acid residues 552 and 554. Mutation at this residue most probably distorts the structure of the Na+ binding site in thrombin. This is the first report indicating the critical role of Arg517 in the normal physiological interaction of thrombin with fibrinogen. This dysprothrombin is designated Prothrombin Greenville. Blood, Vol. 91 No. 6 (March 15), 1998: pp. 2026-2031 © 1998 by The American Society of Hematology. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Marino, Z.-W. Chen, C. E. Ergenekan, L. A. Bush-Pelc, F. S. Mathews, and E. Di Cera Structural Basis of Na+ Activation Mimicry in Murine Thrombin J. Biol. Chem., June 1, 2007; 282(22): 16355 - 16361. [Abstract] [Full Text] [PDF] A. Bah, L. C. Garvey, J. Ge, and E. Di Cera Rapid Kinetics of Na+ Binding to Thrombin J. Biol. Chem., December 29, 2006; 281(52): 40049 - 40056. [Abstract] [Full Text] [PDF] M. J. Page and E. Di Cera Role of na+ and k+ in enzyme function. Physiol Rev, October 1, 2006; 86(4): 1049 - 1092. [Abstract] [Full Text] [PDF] L. A. Bush, R. W. Nelson, and E. Di Cera Murine Thrombin Lacks Na+ Activation but Retains High Catalytic Activity J. Biol. Chem., March 17, 2006; 281(11): 7183 - 7188. [Abstract] [Full Text] [PDF] A. O. Pineda, C. J. Carrell, L. A. Bush, S. Prasad, S. Caccia, Z.-W. Chen, F. S. Mathews, and E. Di Cera Molecular Dissection of Na+ Binding to Thrombin J. Biol. Chem., July 23, 2004; 279(30): 31842 - 31853. [Abstract] [Full Text] [PDF] S. Prasad, K. J. Wright, D. Banerjee Roy, L. A. Bush, A. M. Cantwell, and E. Di Cera Redesigning the monovalent cation specificity of an enzyme PNAS, November 25, 2003; 100(24): 13785 - 13790. [Abstract] [Full Text] [PDF]

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