ID PEZT_STRPN Reviewed; 253 AA. AC Q97QZ1; DT 28-JUN-2011, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2001, sequence version 1. DT 27-MAR-2024, entry version 118. DE RecName: Full=Toxin PezT; DE AltName: Full=UDP-N-acetylglucosamine kinase; DE Short=UNAG kinase; DE EC=2.7.1.176; DE AltName: Full=Zeta toxin; GN Name=pezT; OrderedLocusNames=SP_1051; OS Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4). OC Bacteria; Bacillota; Bacilli; Lactobacillales; Streptococcaceae; OC Streptococcus. OX NCBI_TaxID=170187; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC BAA-334 / TIGR4; RX PubMed=11463916; DOI=10.1126/science.1061217; RA Tettelin H., Nelson K.E., Paulsen I.T., Eisen J.A., Read T.D., RA Peterson S.N., Heidelberg J.F., DeBoy R.T., Haft D.H., Dodson R.J., RA Durkin A.S., Gwinn M.L., Kolonay J.F., Nelson W.C., Peterson J.D., RA Umayam L.A., White O., Salzberg S.L., Lewis M.R., Radune D., RA Holtzapple E.K., Khouri H.M., Wolf A.M., Utterback T.R., Hansen C.L., RA McDonald L.A., Feldblyum T.V., Angiuoli S.V., Dickinson T., Hickey E.K., RA Holt I.E., Loftus B.J., Yang F., Smith H.O., Venter J.C., Dougherty B.A., RA Morrison D.A., Hollingshead S.K., Fraser C.M.; RT "Complete genome sequence of a virulent isolate of Streptococcus RT pneumoniae."; RL Science 293:498-506(2001). RN [2] RP DISRUPTION PHENOTYPE, AND OPERON STRUCTURE. RC STRAIN=0100993 / NCIMB 40794 / Serotype 3; RX PubMed=14977965; DOI=10.1128/iai.72.3.1587-1593.2004; RA Brown J.S., Gilliland S.M., Spratt B.G., Holden D.W.; RT "A locus contained within a variable region of pneumococcal pathogenicity RT island 1 contributes to virulence in mice."; RL Infect. Immun. 72:1587-1593(2004). RN [3] RP SUBUNIT, AND COMPLEX STABILITY. RC STRAIN=ATCC BAA-334 / TIGR4; RX PubMed=20442221; DOI=10.1074/jbc.m110.126250; RA Mutschler H., Reinstein J., Meinhart A.; RT "Assembly dynamics and stability of the pneumococcal epsilon zeta antitoxin RT toxin (PezAT) system from Streptococcus pneumoniae."; RL J. Biol. Chem. 285:21797-21806(2010). RN [4] RP EXPRESSION IN E.COLI, FUNCTION AS A UNAG KINASE, AND MUTAGENESIS OF RP 243-GLY--LYS-253. RC STRAIN=ATCC BAA-334 / TIGR4; RX PubMed=21445328; DOI=10.1371/journal.pbio.1001033; RA Mutschler H., Gebhardt M., Shoeman R.L., Meinhart A.; RT "A novel mechanism of programmed cell death in bacteria by toxin-antitoxin RT systems corrupts peptidoglycan synthesis."; RL PLoS Biol. 9:E1001033-E1001033(2011). RN [5] RP X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS), EXPRESSION IN E.COLI, FUNCTION AS A RP TOXIN, FUNCTION AS A TRANSCRIPTIONAL COREPRESSOR, SUBUNIT, OPERON RP STRUCTURE, AND MUTAGENESIS OF LYS-45; ASP-66; THR-117; THR-120; ARG-157 AND RP ARG-170. RC STRAIN=ATCC BAA-334 / TIGR4; RX PubMed=17488720; DOI=10.1074/jbc.m701703200; RA Khoo S.K., Loll B., Chan W.T., Shoeman R.L., Ngoo L., Yeo C.C., RA Meinhart A.; RT "Molecular and structural characterization of the PezAT chromosomal toxin- RT antitoxin system of the human pathogen Streptococcus pneumoniae."; RL J. Biol. Chem. 282:19606-19618(2007). CC -!- FUNCTION: Toxic component of a type II toxin-antitoxin (TA) system. CC Phosphorylates UDP-N-acetyl-D-glucosamine (UNAG) on the 3'-hydroxyl CC group of the N-acetyl-D-glucosamine moiety, yielding UNAG-3P. UNAG-3P CC inhibits MurA, the first committed step in cell wall synthesis, which CC is then blocked. Upon expression in E.coli results in decreased cell CC growth and viability, followed 3 hours later by growth restoration; the CC toxic effect and phosphorylation of UNAG are neutralized by CC coexpression with cognate antitoxin PezA. A mutant lacking the last 11 CC residues is stably maintained in E.coli, unlike the wild-type which CC undergoes spontaneous mutation. Expression of the deletion mutant in CC rapidly growing liquid cultures leads to cell bulging, permeabilization CC and massive lysis by 1 hour. Cells that survive are not able to undergo CC cytokinesis. Expression in slowly growing cells leads to bulging but CC not lysis. CC -!- FUNCTION: Acts as a corepressor of its own operon with PezA; it is not CC clear if it binds DNA alone. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + UDP-N-acetyl-alpha-D-glucosamine = ADP + H(+) + UDP-N- CC acetyl-alpha-D-glucosamine 3'-phosphate; Xref=Rhea:RHEA:32671, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57705, CC ChEBI:CHEBI:64353, ChEBI:CHEBI:456216; EC=2.7.1.176; CC -!- SUBUNIT: Forms a PezA(2)PezT(2) heterotetramer. The heterotetramer is CC much more stable than either of the proteins alone, and a specific CC mechanism may be necessary to liberate the toxin. CC {ECO:0000269|PubMed:17488720, ECO:0000269|PubMed:20442221}. CC -!- INDUCTION: Conflicting data is available; found to be a member of the CC pezAT operon (upon ectopic expression in E.coli); in S.pneumoniae CC strain 0100993 is found in an operon with the 2 following genes CC (SP_1052 and SP_1053). CC -!- DISRUPTION PHENOTYPE: Strains with a pezT/SP_1052/SP_1053 disruption CC have partially attenuated virulence, they take longer to develop a CC terminal infection in mice, although they grow normally in liquid CC culture. A double SP_1052/SP_1053 disruption grows almost as well as CC wild-type, showing the effect is mostly due to disruption of pezT. CC {ECO:0000269|PubMed:14977965}. CC -!- SIMILARITY: Belongs to the zeta toxin family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AE005672; AAK75165.1; -; Genomic_DNA. DR PIR; D95121; D95121. DR RefSeq; WP_000405360.1; NZ_CP089948.1. DR PDB; 2P5T; X-ray; 3.20 A; B/D/F/H=1-253. DR PDBsum; 2P5T; -. DR AlphaFoldDB; Q97QZ1; -. DR SMR; Q97QZ1; -. DR DIP; DIP-58971N; -. DR IntAct; Q97QZ1; 1. DR PaxDb; 170187-SP_1051; -. DR EnsemblBacteria; AAK75165; AAK75165; SP_1051. DR KEGG; spn:SP_1051; -. DR eggNOG; COG0542; Bacteria. DR PhylomeDB; Q97QZ1; -. DR BioCyc; SPNE170187:G1FZB-1080-MONOMER; -. DR BRENDA; 2.7.1.176; 1960. DR EvolutionaryTrace; Q97QZ1; -. DR Proteomes; UP000000585; Chromosome. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016301; F:kinase activity; IEA:UniProtKB-KW. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR048180; PezT. DR InterPro; IPR010488; Zeta_toxin_domain. DR NCBIfam; NF041574; antitoxPezT_Strep; 1. DR Pfam; PF06414; Zeta_toxin; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. PE 1: Evidence at protein level; KW 3D-structure; ATP-binding; Kinase; Nucleotide-binding; Reference proteome; KW Repressor; Toxin-antitoxin system; Transferase; Virulence. FT CHAIN 1..253 FT /note="Toxin PezT" FT /id="PRO_0000410967" FT ACT_SITE 66 FT /note="Proton acceptor" FT /evidence="ECO:0000305" FT BINDING 39..46 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000305|PubMed:17488720" FT MUTAGEN 45 FT /note="K->A: Abolishes lethality." FT /evidence="ECO:0000269|PubMed:17488720" FT MUTAGEN 66 FT /note="D->T: Abolishes lethality." FT /evidence="ECO:0000269|PubMed:17488720" FT MUTAGEN 117 FT /note="T->V: Abolishes lethality." FT /evidence="ECO:0000269|PubMed:17488720" FT MUTAGEN 120 FT /note="T->V: Very slight reduction in toxic effect." FT /evidence="ECO:0000269|PubMed:17488720" FT MUTAGEN 157 FT /note="R->A: Abolishes lethality." FT /evidence="ECO:0000269|PubMed:17488720" FT MUTAGEN 170 FT /note="R->A: Abolishes lethality." FT /evidence="ECO:0000269|PubMed:17488720" FT MUTAGEN 243..253 FT /note="Missing: Retains toxicity while being stably FT maintained in E.coli." FT /evidence="ECO:0000269|PubMed:21445328" FT HELIX 8..23 FT /evidence="ECO:0007829|PDB:2P5T" FT STRAND 33..39 FT /evidence="ECO:0007829|PDB:2P5T" FT HELIX 41..43 FT /evidence="ECO:0007829|PDB:2P5T" FT HELIX 46..55 FT /evidence="ECO:0007829|PDB:2P5T" FT TURN 56..58 FT /evidence="ECO:0007829|PDB:2P5T" FT STRAND 61..63 FT /evidence="ECO:0007829|PDB:2P5T" FT HELIX 65..69 FT /evidence="ECO:0007829|PDB:2P5T" FT HELIX 75..79 FT /evidence="ECO:0007829|PDB:2P5T" FT HELIX 87..107 FT /evidence="ECO:0007829|PDB:2P5T" FT STRAND 112..115 FT /evidence="ECO:0007829|PDB:2P5T" FT HELIX 122..133 FT /evidence="ECO:0007829|PDB:2P5T" FT STRAND 137..143 FT /evidence="ECO:0007829|PDB:2P5T" FT HELIX 147..160 FT /evidence="ECO:0007829|PDB:2P5T" FT TURN 161..163 FT /evidence="ECO:0007829|PDB:2P5T" FT HELIX 181..193 FT /evidence="ECO:0007829|PDB:2P5T" FT STRAND 198..203 FT /evidence="ECO:0007829|PDB:2P5T" FT STRAND 209..212 FT /evidence="ECO:0007829|PDB:2P5T" FT TURN 213..215 FT /evidence="ECO:0007829|PDB:2P5T" FT HELIX 220..229 FT /evidence="ECO:0007829|PDB:2P5T" FT HELIX 234..250 FT /evidence="ECO:0007829|PDB:2P5T" SQ SEQUENCE 253 AA; 29129 MW; 0F7CD8D0B26EE89E CRC64; MEIQDYTDSE FKHALARNLR SLTRGKKSSK QPIAILLGGQ SGAGKTTIHR IKQKEFQGNI VIIDGDSFRS QHPHYLELQQ EYGKDSVEYT KDFAGKMVES LVTKLSSLRY NLLIEGTLRT VDVPKKTAQL LKNKGYEVQL ALIATKPELS YLSTLIRYEE LYIINPNQAR ATPKEHHDFI VNHLVDNTRK LEELAIFERI QIYQRDRSCV YDSKENTTSA ADVLQELLFG EWSQVEKEML QVGEKRLNEL LEK //