Q97QZ1 (PEZT_STRPN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Toxin PezT

Alternative name(s):
UDP-N-acetylglucosamine kinase
Short name=UNAG kinase
EC=2.7.1.176
Zeta toxin

Gene names

Name:	pezT
Ordered Locus Names:	SP_1051

Organism

Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4) [Complete proteome] [HAMAP]

Taxonomic identifier

170187 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Firmicutes › Bacilli › Lactobacillales › Streptococcaceae › Streptococcus › Streptococcus pneumoniae

Protein attributes

Sequence length	253 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Toxic component of a toxin-antitoxin (TA) module. Phosphorylates UDP-N-acetyl-D-glucosamine (UNAG) on the 3'-hydroxyl group of the N-acetyl-D-glucosamine moiety, yielding UNAG-3P. UNAG-3P inhibits MurA, the first committed step in cell wall synthesis, which is then blocked. Upon expression in E.coli results in decreased cell growth and viability, followed 3 hours later by growth restoration; the toxic effect and phosphorylation of UNAG are neutralized by coexpression with cognate antitoxin PezA. A mutant lacking the last 11 residues is stably maintained in E.coli, unlike the wild-type which undergoes spontaneous mutation. Expression of the deletion mutant in rapidly growing liquid cultures leads to cell bulging, permeabilization and massive lysis by 1 hour. Cells that survive are not able to undergo cytokinesis. Expression in slowly growing cells leads to bulging but not lysis. Ref.4 Ref.5 Acts as a corepressor of its own operon with PezA; it is not clear if it binds DNA alone. Ref.4 Ref.5
Catalytic activity	ATP + UDP-N-acetyl-alpha-D-glucosamine = ADP + UDP-N-acetyl-alpha-D-glucosamine 3'-phosphate.
Subunit structure	Forms a PezA2PezT2 heterotetramer. The heterotetramer is much more stable than either of the proteins alone, and a specific mechanism may be necessary to liberate the toxin. Ref.3 Ref.5
Induction	Conflicting data is available; found to be a member of the pezAT operon (upon ectopic expression in E.coli); in S.pneumoniae strain 0100993 is found in an operon with the 2 following genes (SP_1052 and SP_1053).
Disruption phenotype	Strains with a pezT/SP_1052/SP_1053 disruption have partially attenuated virulence, they take longer to develop a terminal infection in mice, although they grow normally in liquid culture. A double SP_1052/SP_1053 disruption grows almost as well as wild-type, showing the effect is mostly due to disruption of pezT. Ref.2
Sequence similarities	Belongs to the zeta toxin family.

Ontologies

Keywords
Biological process	Virulence
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Repressor Toxin Transferase
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological_process	pathogenesis Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 253

253

Toxin PezT

PRO_0000410967

Regions

Nucleotide binding

39 – 46

8

ATP Potential

Sites

Active site

66

1

Proton acceptor Probable

Experimental info

Mutagenesis

45

1

K → A: Abolishes lethality. Ref.5

Mutagenesis

66

1

D → T: Abolishes lethality. Ref.5

Mutagenesis

117

1

T → V: Abolishes lethality. Ref.5

Mutagenesis

120

1

T → V: Very slight reduction in toxic effect. Ref.5

Mutagenesis

157

1

R → A: Abolishes lethality. Ref.5

Mutagenesis

170

1

R → A: Abolishes lethality. Ref.5

Mutagenesis

243 – 253

11

Missing: Retains toxicity while being stably maintained in E.coli. Ref.4

Secondary structure

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253

Helix Strand Turn

Details...

Helix

8 – 23

16

Beta strand

33 – 39

7

Helix

41 – 43

3

Helix

46 – 55

10

Turn

56 – 58

3

Beta strand

61 – 63

3

Helix

65 – 69

5

Helix

75 – 79

5

Helix

87 – 107

21

Beta strand

112 – 115

4

Helix

122 – 133

12

Beta strand

137 – 143

7

Helix

147 – 160

14

Turn

161 – 163

3

Helix

181 – 193

13

Beta strand

198 – 203

6

Beta strand

209 – 212

4

Turn

213 – 215

3

Helix

220 – 229

10

Helix

234 – 250

17

Sequences

	Sequence		Length	Mass (Da)
	Q97QZ1 [UniParc]. Last modified October 1, 2001. Version 1. Checksum: 0F7CD8D0B26EE89E	FASTA	253	29,129
	10 20 30 40 50 60 MEIQDYTDSE FKHALARNLR SLTRGKKSSK QPIAILLGGQ SGAGKTTIHR IKQKEFQGNI 70 80 90 100 110 120 VIIDGDSFRS QHPHYLELQQ EYGKDSVEYT KDFAGKMVES LVTKLSSLRY NLLIEGTLRT 130 140 150 160 170 180 VDVPKKTAQL LKNKGYEVQL ALIATKPELS YLSTLIRYEE LYIINPNQAR ATPKEHHDFI 190 200 210 220 230 240 VNHLVDNTRK LEELAIFERI QIYQRDRSCV YDSKENTTSA ADVLQELLFG EWSQVEKEML 250 QVGEKRLNEL LEK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete genome sequence of a virulent isolate of Streptococcus pneumoniae." Tettelin H., Nelson K.E., Paulsen I.T., Eisen J.A., Read T.D., Peterson S.N., Heidelberg J.F., DeBoy R.T., Haft D.H., Dodson R.J., Durkin A.S., Gwinn M.L., Kolonay J.F., Nelson W.C., Peterson J.D., Umayam L.A., White O., Salzberg S.L. , Lewis M.R., Radune D., Holtzapple E.K., Khouri H.M., Wolf A.M., Utterback T.R., Hansen C.L., McDonald L.A., Feldblyum T.V., Angiuoli S.V., Dickinson T., Hickey E.K., Holt I.E., Loftus B.J., Yang F., Smith H.O., Venter J.C., Dougherty B.A., Morrison D.A., Hollingshead S.K., Fraser C.M. Science 293:498-506(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC BAA-334 / TIGR4.
[2]	"A locus contained within a variable region of pneumococcal pathogenicity island 1 contributes to virulence in mice." Brown J.S., Gilliland S.M., Spratt B.G., Holden D.W. Infect. Immun. 72:1587-1593(2004) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE, OPERON STRUCTURE. Strain: 0100993 / NCIMB 40794 / Serotype 3.
[3]	"Assembly dynamics and stability of the pneumococcal epsilon zeta antitoxin toxin (PezAT) system from Streptococcus pneumoniae." Mutschler H., Reinstein J., Meinhart A. J. Biol. Chem. 285:21797-21806(2010) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT, COMPLEX STABILITY. Strain: ATCC BAA-334 / TIGR4.
[4]	"A novel mechanism of programmed cell death in bacteria by toxin-antitoxin systems corrupts peptidoglycan synthesis." Mutschler H., Gebhardt M., Shoeman R.L., Meinhart A. PLoS Biol. 9:E1001033-E1001033(2011) [PubMed] [Europe PMC] [Abstract] Cited for: EXPRESSION IN E.COLI, FUNCTION AS A UNAG KINASE, MUTAGENESIS OF 243-GLY--LYS-253. Strain: ATCC BAA-334 / TIGR4.
[5]	"Molecular and structural characterization of the PezAT chromosomal toxin-antitoxin system of the human pathogen Streptococcus pneumoniae." Khoo S.K., Loll B., Chan W.T., Shoeman R.L., Ngoo L., Yeo C.C., Meinhart A. J. Biol. Chem. 282:19606-19618(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS), EXPRESSION IN E.COLI, FUNCTION AS A TOXIN, FUNCTION AS A TRANSCRIPTIONAL COREPRESSOR, SUBUNIT, OPERON STRUCTURE, MUTAGENESIS OF LYS-45; ASP-66; THR-117; THR-120; ARG-157 AND ARG-170. Strain: ATCC BAA-334 / TIGR4.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AE005672 Genomic DNA. Translation: AAK75165.1.

PIR

D95121.

RefSeq

NP_345525.1. NC_003028.3.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2P5T	X-ray	3.20	B/D/F/H	1-253	[»]

ProteinModelPortal

Q97QZ1.

SMR

Q97QZ1. Positions 1-251.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-58971N.

STRING

170187.SP_1051.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAK75165; AAK75165; SP_1051.

GeneID

931565.

KEGG

spn:SP_1051.

PATRIC

19706509. VBIStrPne105772_1099.

Organism-specific databases

CMR

Search...

Phylogenomic databases

HOGENOM

HOG000267564.

KO

K16214.

OMA

MLMATLM.

ProtClustDB

CLSK803780.

Family and domain databases

InterPro

IPR010488. Zeta_toxin_domain.
[Graphical view]

Pfam

PF06414. Zeta_toxin. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q97QZ1.

Entry information

Entry name

PEZT_STRPN

Accession

Primary (citable) accession number: Q97QZ1

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 28, 2011
Last sequence update:	October 1, 2001
Last modified:	May 1, 2013
This is version 69 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program