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Title
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Tissue-type plasminogen activator: variants and crystal/solution structures demarcate structural determinants of function.
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Authors
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W.Bode,
M.Renatus.
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Ref.
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Curr Opin Struct Biol, 1997,
7,
865-872.
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PubMed id
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Abstract
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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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