TY - JOUR
T1 - Converting tissue plasminogen activator to a zymogen
T2 - A regulatory triad of Asp-His-Ser
AU - Madison, Edwin L.
AU - Kobe, Andreja
AU - Gething, Mary Jane
AU - Sambrook, Joseph F.
AU - Goldsmith, Elizabeth J.
PY - 1993
Y1 - 1993
N2 - Unlike most serine proteases of the chymotrypsin family, tissue-type plasminogen activator (tPA) is secreted from cells as an active, single-chain enzyme with a catalytic efficiency only slightly lower than that of the proteolytically cleaved form. A zymogenic mutant of tPA has been engineered that displays a reduction in catalytic efficiency by a factor of 141 in the single-chain form while retaining full activity in the cleaved form. The residues introduced in the mutant, serine 292 and histidine 305, are proposed to form a hydrogen-bonded network with aspartate 477, similar to the aspartate 194-histidine 40-serine 32 network found to stabilize the zymogen chymotrypsinogen.
AB - Unlike most serine proteases of the chymotrypsin family, tissue-type plasminogen activator (tPA) is secreted from cells as an active, single-chain enzyme with a catalytic efficiency only slightly lower than that of the proteolytically cleaved form. A zymogenic mutant of tPA has been engineered that displays a reduction in catalytic efficiency by a factor of 141 in the single-chain form while retaining full activity in the cleaved form. The residues introduced in the mutant, serine 292 and histidine 305, are proposed to form a hydrogen-bonded network with aspartate 477, similar to the aspartate 194-histidine 40-serine 32 network found to stabilize the zymogen chymotrypsinogen.
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U2 - 10.1126/science.8211162
DO - 10.1126/science.8211162
M3 - Article
C2 - 8211162
AN - SCOPUS:0027496219
SN - 0036-8075
VL - 262
SP - 419
EP - 421
JO - Science
JF - Science
IS - 5132
ER -