title: Elucidation of the cause for reduced activity of abnormal human plasmin containing an Ala55-Thr mutation: importance of highly conserved Ala55 in serine proteases.
abstract: In serine proteases, Ala55 is highly conserved and located just behind the catalytic triad. That the activity of human plasmin is reduced by the A55T substitution indicates the importance of Ala55 in catalysis. In the present study, the 3-D model of A55T human plasmin shows that an unusual hydrogen bond between Thr55 Ogamma1 and His57 Nepsilon2 alters His57 into an inactive conformation in which His57 cannot accept a proton from Ser195 as a catalytic base. Our results demonstrate that Ala55 contributes heavily to the active conformation of His57 and ensures the proton transfer from Ser195 to His57.
authors.affiliation: School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan. shitakam@platinum.pharm.kitasato-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Takeda-Shitaka
authors.forename: H
authors.initials: H
authors.lastname: Umeyama
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002384:Catalysis; D002417:Cattle; D017124:Conserved Sequence / Q000235:genetics; D005341:Fibrinolysin / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000737:chemistry*; D014357:Trypsin / Q000737:chemistry
chemical_list: D012697:Serine Endopeptidases; D014357:Trypsin; D005341:Fibrinolysin