FEBS Letters · 1983 · 63 citations · 14 references
Life SciencesBiochemistryMolecular BiologyEnzymologyProtein BiochemistryStructural BiologyDisulfide Bond FormationProtein DomainsProtein MotifsProtein StructureProteolytic EnzymesStructural EnzymologyBinding Pocket GeometryEnzyme-inhibitor BindingExtracellular ProteasesPlasminogen ActivatorsProtease EvolutionProtease FamiliesProtease Structure Function RelationshipsProtease Substrate Specificity
The sequences of urokinase (UK) and tissue-type plasminogen activator (TPA) were aligned with those of chymotrypsin, trypsin, and elastase according to their 'structurally conserved regions'. In spite of its trypsin-like specificity UK was model-built on the basis of the chymotrypsin structure because of a corresponding disulfide pattern. The extra disulfide bond falls to cysteines 50 and 111d. Insertions can easily be accommodated at the surface. As they occur similarly in both, UK and TPA, a role in plasminogen recognition may be possible. Of the functional positions known to be involved in substrate or inhibitor binding, Asp 97, Lys 143 and Arg 217 (Leu in TPA) may contribute to plasminogen activating specificity. PTI binding may in part be impaired by structural differences at the edge of the binding pocket.
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Atlas of Protein Sequence and Structure, 1972.
Walter M. Fitch, M. O. Dayhoff · Systematic Zoology · 1973 · 2.5K citations
Cloning and expression of human tissue-type plasminogen activator cDNA in E. coli
Diane Pennica, William E. Holmes, William J. Kohr et al. · Nature · 1983 · 1.2K citations