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PubMed:11598120 JSONTXT

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Id Subject Object Predicate Lexical cue
T1 0-111 Sentence denotes Multiple activation loop conformations and their regulatory properties in the insulin receptor's kinase domain.
T2 112-253 Sentence denotes Low catalytic efficiency of protein kinases often results from intrasteric inhibition caused by the activation loop blocking the active site.
T3 254-457 Sentence denotes In the insulin receptor's kinase domain, Asp-1161 and Tyr-1162 in the peptide substrate-like sequence of the unphosphorylated activation loop can interact with four invariant residues in the active site:
T4 458-501 Sentence denotes Lys-1085, Asp-1132, Arg-1136, and Gln-1208.
T5 502-651 Sentence denotes Contributions of these six residues to intrasteric inhibition were tested by mutagenesis, and the unphosphorylated kinase domains were characterized.
T6 652-823 Sentence denotes The mutations Q1208S, K1085N, and Y1162F each relieved intrasteric inhibition, increasing catalytic efficiency but without changing the rate-limiting step of the reaction.
T7 824-878 Sentence denotes The mutants R1136Q and D1132N were virtually inactive.
T8 879-1060 Sentence denotes Steric accessibility of the active site was ranked by relative changes in iodide quenching of intrinsic fluorescence, and A-loop conformation was ranked by limited tryptic cleavage.
T9 1061-1222 Sentence denotes Together these ranked the openness of the active site cleft as R1136Q approximately D1132N > or = D1161A > Y1162F approximately K1085N > Q1208S > or = wild-type.
T10 1223-1427 Sentence denotes These findings demonstrate the importance of specific invariant residues for intrasteric inhibition and show that diverse activation loop conformations can produce similar steady-state kinetic properties.
T11 1428-1578 Sentence denotes This suggests a broader range of regulatory properties for the activation loop than expected from a simple off-versus-on switch for kinase activation.