TET_PYRHO
ID TET_PYRHO Reviewed; 353 AA.
AC O59196;
DT 09-FEB-2010, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Tetrahedral aminopeptidase;
DE Short=TET;
DE Short=TET aminopeptidase;
DE EC=3.4.11.-;
DE AltName: Full=Leucyl aminopeptidase;
DE AltName: Full=PhTET2;
GN Name=frvX; OrderedLocusNames=PH1527;
OS Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC
OS 100139 / OT-3).
OC Archaea; Euryarchaeota; Thermococci; Thermococcales; Thermococcaceae;
OC Pyrococcus.
OX NCBI_TaxID=70601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3;
RX PubMed=9679194; DOI=10.1093/dnares/5.2.55;
RA Kawarabayasi Y., Sawada M., Horikawa H., Haikawa Y., Hino Y., Yamamoto S.,
RA Sekine M., Baba S., Kosugi H., Hosoyama A., Nagai Y., Sakai M., Ogura K.,
RA Otsuka R., Nakazawa H., Takamiya M., Ohfuku Y., Funahashi T., Tanaka T.,
RA Kudoh Y., Yamazaki J., Kushida N., Oguchi A., Aoki K., Yoshizawa T.,
RA Nakamura Y., Robb F.T., Horikoshi K., Masuchi Y., Shizuya H., Kikuchi H.;
RT "Complete sequence and gene organization of the genome of a hyper-
RT thermophilic archaebacterium, Pyrococcus horikoshii OT3.";
RL DNA Res. 5:55-76(1998).
RN [2]
RP FUNCTION AS AN AMINOPEPTIDASE, CATALYTIC ACTIVITY, COFACTOR, SUBSTRATE
RP SPECIFICITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT,
RP AND REACTION MECHANISM.
RX PubMed=15736957; DOI=10.1021/bi047736j;
RA Dura M.A., Receveur-Brechot V., Andrieu J.P., Ebel C., Schoehn G.,
RA Roussel A., Franzetti B.;
RT "Characterization of a TET-like aminopeptidase complex from the
RT hyperthermophilic archaeon Pyrococcus horikoshii.";
RL Biochemistry 44:3477-3486(2005).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) IN COMPLEX WITH ZINC IONS, FUNCTION
RP AS AN AMINOPEPTIDASE, CATALYTIC ACTIVITY, COFACTOR, SUBUNIT, ACTIVE SITE,
RP AND CATALYTIC MECHANISM.
RX PubMed=15375159; DOI=10.1074/jbc.m409455200;
RA Russo S., Baumann U.;
RT "Crystal structure of a dodecameric tetrahedral-shaped aminopeptidase.";
RL J. Biol. Chem. 279:51275-51281(2004).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEXES WITH ZINC IONS AND THE
RP INHIBITOR AMASTATIN, FUNCTION IN PROTEIN DEGRADATION, COFACTOR, SUBUNIT,
RP ACTIVE SITE, AND CATALYTIC MECHANISM.
RX PubMed=15713475; DOI=10.1016/j.jmb.2004.12.056;
RA Borissenko L., Groll M.;
RT "Crystal structure of TET protease reveals complementary protein
RT degradation pathways in prokaryotes.";
RL J. Mol. Biol. 346:1207-1219(2005).
CC -!- FUNCTION: Functions as an aminopeptidase, with a clear preference for
CC leucine as the N-terminal amino acid. However, can also cleave
CC moderately long polypeptide substrates of various compositions in a
CC fairly unspecific manner. Has neither carboxypeptidase nor
CC endoproteolytic activities, and it is devoid of N-terminal deblocking
CC activity. Is involved in protein degradation, performing degradation of
CC oligopeptides produced by the proteasome into single amino acids.
CC {ECO:0000269|PubMed:15375159, ECO:0000269|PubMed:15713475,
CC ECO:0000269|PubMed:15736957}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:15375159, ECO:0000269|PubMed:15713475,
CC ECO:0000269|PubMed:15736957};
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000269|PubMed:15375159, ECO:0000269|PubMed:15713475,
CC ECO:0000269|PubMed:15736957};
CC Note=Binds 2 Zn(2+) ions per subunit. Can also use Co(2+).
CC {ECO:0000269|PubMed:15375159, ECO:0000269|PubMed:15713475,
CC ECO:0000269|PubMed:15736957};
CC -!- ACTIVITY REGULATION: Inhibited by EDTA and bestatin in vitro. Is
CC insensitive to papain, antipain, chymostatin, leupeptin, pepstatin and
CC aprotinin. {ECO:0000269|PubMed:15736957}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.5 with Leu-pNA as substrate. Strong activity is still
CC detectable at pH 6 and 9. {ECO:0000269|PubMed:15736957};
CC Temperature dependence:
CC Optimum temperature is 100 degrees Celsius over a broad pH array. At
CC temperatures lower than 70 degrees Celsius, less than 10% of the
CC maximum activity is detected. Highly thermostable. Shows half-lives
CC of 24.8 minutes and 10.03 hours when incubated at 100 and 80 degrees
CC Celsius, respectively. {ECO:0000269|PubMed:15736957};
CC -!- SUBUNIT: Homododecamer. The assembly of six dimers results in a
CC tetrahedral-shaped structure; all 12 active sites are located on the
CC inside of the tetrahedron. Substrate access is granted by four pores
CC with a maximal diameter of 18 Angstroms, allowing only small peptides
CC and unfolded proteins access to the active site. Beside the four entry
CC ports, TET contains 12 small product release openings, which are large
CC enough to allow passage of only single amino acid residues.
CC {ECO:0000269|PubMed:15375159, ECO:0000269|PubMed:15713475,
CC ECO:0000269|PubMed:15736957}.
CC -!- MISCELLANEOUS: The hydrolytic mechanism is nonprocessive. Therefore,
CC the enzyme does not process one substrate molecule completely before
CC starting with another one. Instead, the reaction products are generated
CC by multiple rounds of substrate digestion.
CC -!- SIMILARITY: Belongs to the peptidase M42 family. {ECO:0000305}.
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DR EMBL; BA000001; BAA30637.1; -; Genomic_DNA.
DR PIR; E71029; E71029.
DR PDB; 1XFO; X-ray; 1.96 A; A/B/C/D=1-353.
DR PDB; 1Y0R; X-ray; 1.75 A; A=1-353.
DR PDB; 1Y0Y; X-ray; 1.60 A; A=1-353.
DR PDB; 6F3K; Other; 4.10 A; A=1-353.
DR PDB; 6R8N; Other; 4.10 A; A/B/C/D/E/F/G/H/I/J/K/L=1-353.
DR PDBsum; 1XFO; -.
DR PDBsum; 1Y0R; -.
DR PDBsum; 1Y0Y; -.
DR PDBsum; 6F3K; -.
DR PDBsum; 6R8N; -.
DR AlphaFoldDB; O59196; -.
DR BMRB; O59196; -.
DR SMR; O59196; -.
DR STRING; 70601.3257954; -.
DR MEROPS; M42.004; -.
DR EnsemblBacteria; BAA30637; BAA30637; BAA30637.
DR KEGG; pho:PH1527; -.
DR eggNOG; arCOG01518; Archaea.
DR OMA; FGWPAIH; -.
DR BRENDA; 3.4.11.1; 5244.
DR BRENDA; 3.4.11.B4; 5244.
DR BRENDA; 3.4.11.B9; 5244.
DR EvolutionaryTrace; O59196; -.
DR Proteomes; UP000000752; Chromosome.
DR GO; GO:0004177; F:aminopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008237; F:metallopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 2.40.30.40; -; 1.
DR InterPro; IPR008007; Peptidase_M42.
DR InterPro; IPR023367; Peptidase_M42_dom2.
DR Pfam; PF05343; Peptidase_M42; 1.
DR PIRSF; PIRSF001123; PepA_GA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aminopeptidase; Cobalt; Hydrolase; Metal-binding;
KW Metalloprotease; Protease; Zinc.
FT CHAIN 1..353
FT /note="Tetrahedral aminopeptidase"
FT /id="PRO_0000391012"
FT ACT_SITE 212
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:15375159,
FT ECO:0000269|PubMed:15713475"
FT BINDING 68
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 182
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 182
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT BINDING 213
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT BINDING 235
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 323
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT HELIX 9..17
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT HELIX 25..27
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT HELIX 29..37
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT HELIX 38..40
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT STRAND 41..46
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT STRAND 52..56
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT STRAND 62..68
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT STRAND 73..79
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT STRAND 85..92
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT HELIX 95..97
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT TURN 98..100
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT STRAND 102..108
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT STRAND 111..118
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT HELIX 136..138
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT STRAND 140..142
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT HELIX 148..153
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT STRAND 161..164
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT STRAND 169..171
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT TURN 172..174
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT STRAND 175..178
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT HELIX 181..196
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT STRAND 201..210
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT TURN 213..215
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT HELIX 217..226
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT STRAND 229..238
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT HELIX 247..249
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT STRAND 258..264
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT HELIX 271..283
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT STRAND 288..292
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT HELIX 300..303
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT STRAND 312..321
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT STRAND 323..325
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT STRAND 327..330
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT HELIX 331..347
FT /evidence="ECO:0007829|PDB:1Y0Y"
FT HELIX 348..350
FT /evidence="ECO:0007829|PDB:1Y0Y"
SQ SEQUENCE 353 AA; 39014 MW; A6AE25809C8B2041 CRC64;
MEVRNMVDYE LLKKVVEAPG VSGYEFLGIR DVVIEEIKDY VDEVKVDKLG NVIAHKKGEG
PKVMIAAHMD QIGLMVTHIE KNGFLRVAPI GGVDPKTLIA QRFKVWIDKG KFIYGVGASV
PPHIQKPEDR KKAPDWDQIF IDIGAESKEE AEDMGVKIGT VITWDGRLER LGKHRFVSIA
FDDRIAVYTI LEVAKQLKDA KADVYFVATV QEEVGLRGAR TSAFGIEPDY GFAIDVTIAA
DIPGTPEHKQ VTHLGKGTAI KIMDRSVICH PTIVRWLEEL AKKHEIPYQL EILLGGGTDA
GAIHLTKAGV PTGALSVPAR YIHSNTEVVD ERDVDATVEL MTKALENIHE LKI
