PMID: 9434908Jan 22, 1998Paper

Tissue-type plasminogen activator: variants and crystal/solution structures demarcate structural determinants of function

Current Opinion in Structural Biology
W Bode, M Renatus

Abstract

NMR and crystal structure of many components of tissue-type plasminogen activator (t-PA) are now available: the finger-EGF pair and the kringle-2 domain structures have been solved, as have the proteolytic domains of vampire bat PA and human t-PA in two- and single-chain forms. These structures confirm the trypsin-like arrangement of the proteolytic domain of t-PA and show how surface loops near the catalytic centre contribute to the narrow specificity of t-PA. Together with mutational experiments, they identify the Lys156 sidechain as a cause of the amidolytic activity of single-chain t-PA, as it can provide a substitute salt bridge partner for Asp194 in the absence of the Ile16 N terminus of the two-chain form. These new findings provide new ideas for the design of PA variants with improved therapeutic properties.

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Citations

May 6, 1998·Protein Science : a Publication of the Protein Society·A R Khan, M N James
Sep 16, 2008·Die Naturwissenschaften·Asa Tellgren-RothDavid A Liberles
Feb 9, 2000·Trends in Biochemical Sciences·M A ParryI Bode
Apr 2, 1999·European Journal of Biochemistry·H Czapinska, J Otlewski
Dec 4, 2004·Proteins·Olgun GuvenchCharles L Brooks
Nov 20, 2008·Journal of Thrombosis and Haemostasis : JTH·D C Rijken, H R Lijnen
Apr 18, 2001·Genome Biology·D A LiberlesS A Benner
Mar 14, 2012·Toxicon : Official Journal of the International Society on Toxinology·Rodrigo Ligabue-BraunCélia Regina Carlini
Jan 23, 2003·The Journal of Thoracic and Cardiovascular Surgery·Elizabeth N MorganEdward D Verrier
Apr 18, 2013·Orthopedics·Patrick Orth, Konstantinos Anagnostakos
Mar 20, 1999·The Journal of Biological Chemistry·H R StennickeG S Salvesen
Jul 31, 2019·Computational and Structural Biotechnology Journal·Jan MicanJiri Damborsky

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