(Below N is a link to NCBI taxonomic web page and E link to ESTHER at designed phylum.) > cellular organisms: NE > Archaea: NE > Euryarchaeota: NE > Thermoplasmata: NE > Thermoplasmatales: NE > Thermoplasmataceae: NE > Thermoplasma: NE > Thermoplasma acidophilum: NE
No mutation 14 structures(e.g. : 1MT3, 1MTZ, 1MU0... more)(less) 1MT3: Crystal Structure Of The Tricorn Interacting Factor Selenomethionine-F1, 1MTZ: Crystal Structure Of The Tricorn Interacting Factor F1, 1MU0: Crystal Structure Of The Tricorn Interacting Factor F1 Complex With Pck, 1XQV: Crystal structure of inactive tricorn-interacting factor F1-mutant G37A, 1XQW: Crystal structure of tricorn-interacting factor F1-mutant S105A complex with PHE-LEU, 1XQX: Crystal structure of tricorn-interacting factor F1-mutant S105A complex with PCK, 1XQY: Crystal structure of tricorn-interacting factor F1-mutant S105A complex with PRO-LEU-GLY-GLY, 1XRL: Crystal structure of active site tricorn-interacting factor F1-mutant Y205F complex with inhibitor PCK, 1XRM: Crystal structure of active site tricorn-interacting factor F1-mutant E213Q soaked with peptide Ala-Phe, 1XRN: Crystal structure of active site tricorn-interacting factor F1-mutant E213Q soaked with peptide Phe-Ala, 1XRO: Crystal structure of active site tricorn-interacting factor F1-mutant E213Q soaked with peptide Phe-Leu, 1XRP: Crystal structure of active site tricorn-interacting factor F1-mutant E213Q soaked with peptide Pro-Leu-Gly-Gly, 1XRQ: Crystal structure of active site tricorn-interacting factor F1-mutant E245Q soaked with peptide Phe-Leu, 1XRR: Crystal structure of active site tricorn-interacting factor F1-mutant E245Q soaked with peptide Pro-Pro No kinetic
LegendThis sequence has been compared to family alignement (MSA) red => minority aminoacid blue => majority aminoacid color intensity => conservation rate title => sequence position(MSA position)aminoacid rate Catalytic site Catalytic site in the MSA MDQECIENYAKVNGIYIYYKLCKAPEEKAKLMTMHGGPGMSHDYLLSLRD MTKEGITVLFYDQFGCGRSEEPDQSKFTIDYGVEEAEALRSKLFGNEKVF LMGSSYGGALALAYAVKYQDHLKGLIVSGGLSSVPLTVKEMNRLIDELPA KYRDAIKKYGSSGSYENPEYQEAVNYFYHQHLLRSEDWPPEVLKSLEYAE RRNVYRIMNGPNEFTITGTIKDWDITDKISAIKIPTLITVGEYDEVTPNV ARVIHEKIAGSELHVFRDCSHLTMWEDREGYNKLLSDFILKHL
The tricorn-interacting factor F1 of the archaeon Thermoplasma acidophilum cleaves small hydrophobic peptide products of the proteasome and tricorn protease. F1 mutants of the active site residues that are involved in substrate recognition and catalysis displayed distinct activity patterns toward fluorogenic test substrates. Crystal structures of the mutant proteins complexed with peptides Phe-Leu, Pro-Pro, or Pro-Leu-Gly-Gly showed interaction of glutamates 213 and 245 with the N termini of the peptides and defined the S1 and S1' sites and the role of the catalytic residues. Evidence was found for processive peptide cleavage in the N-to-C direction, whereby the P1' product is translocated into the S1 site. A functional interaction of F1 with the tricorn protease was observed with the inactive F1 mutant G37A. Moreover, small angle x-ray scattering measurements for tricorn and inhibited F1 have been interpreted as formation of transient and substrate-induced complexes.
Title: Structures of the tricorn-interacting aminopeptidase F1 with different ligands explain its catalytic mechanism Goettig P, Groll M, Kim JS, Huber R, Brandstetter H Ref: EMBO Journal, 21:5343, 2002 : PubMed
F1 is a 33.5 kDa serine peptidase of the alpha/beta-hydrolase family from the archaeon Thermoplasma acidophilum. Subsequent to proteasomal protein degradation, tricorn generates small peptides, which are cleaved by F1 to yield single amino acids. We have solved the crystal structure of F1 with multiwavelength anomalous dispersion (MAD) phasing at 1.8 A resolution. In addition to the conserved catalytic domain, the structure reveals a chiefly alpha-helical domain capping the catalytic triad. Thus, the active site is accessible only through a narrow opening from the protein surface. Two structures with molecules bound to the active serine, including the inhibitor phenylalanyl chloromethylketone, elucidate the N-terminal recognition of substrates and the catalytic activation switch mechanism of F1. The cap domain mainly confers the specificity for hydrophobic side chains by a novel cavity system, which, analogously to the tricorn protease, guides substrates to the buried active site and products away from it. Finally, the structure of F1 suggests a possible functional complex with tricorn that allows efficient processive degradation to free amino acids for cellular recycling.
Title: Tricorn protease (TRI) interacting factor 1 from Thermoplasma acidophilum is a proline iminopeptidase Tamura T, Tamura N, Lottspeich F, Baumeister W Ref: FEBS Letters, 398:101, 1996 : PubMed
Tricorn protease (TRI), a high molecular mass complex from the archaeon T. acidophilum, forms the core of a modular proteolytic system; upon interacting with low molecular mass factors intrinsic activities are enhanced and novel activities are generated. Here we characterize the first factor, F1, which turns out to be homologous with several bacterial proline iminopeptidases (PIPs). Surprisingly, it cleaves not only typical PIP substrates such as H-Pro-AMC, but a wide spectrum of amino acid substrates and several peptide substrates without a proline at the N-terminus. The pip gene encodes a 293 amino acid residue protein with a molecular mass of 33,487 Da. By means of site-directed mutagenesis we identified Ser105 and His271 as the active site nucleophile and proton donor, respectively. Experiments with inactive mutant PIPs indicate that the activities elicited by interacting with TRI are contributed by PIP.
Thermoplasma acidophilum proline iminopeptidase gene
