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Protein

Bifunctional (p)ppGpp synthase/hydrolase RelA

Gene

relA

Organism
Streptococcus dysgalactiae subsp. equisimilis (Streptococcus equisimilis)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

In eubacteria ppGpp (guanosine 3'-diphosphate 5-' diphosphate) is a mediator of the stringent response that coordinates a variety of cellular activities in response to changes in nutritional abundance. This enzyme catalyzes both the formation of pppGpp which is then hydrolyzed to form ppGpp, and the hydrolysis of ppGpp. The enzyme does not simultaneously display both synthase and hydrolase activities. In the structure of residues 1-385 there are 2 conformations seen, the hydrolase-OFF/synthase-ON and hydrolase-ON/synthase-OFF, suggesting there is ligand-induced signal transmission between the 2 active sites.

Catalytic activityi

ATP + GTP = AMP + guanosine 3'-diphosphate 5'-triphosphate.
Guanosine 3',5'-bis(diphosphate) + H2O = guanosine 5'-diphosphate + diphosphate.

Cofactori

Protein has several cofactor binding sites:
  • Mg2+CuratedNote: Binds 1 Mg2+ ion per subunit.Curated
  • Mn2+1 PublicationNote: Binds 1 Mn2+ ion per subunit.1 Publication

Enzyme regulationi

Alpha-beta methylenyl ATP, an ATP-analog inhibitor of the synthase activity also reduces the hydrolase activity about 4-fold.2 Publications

Kineticsi

  1. KM=2 mM for GTP1 Publication
  2. KM=5 mM for ATP1 Publication

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi53 – 531Manganese
Metal bindingi77 – 771Manganese
Active sitei81 – 811Nucleophile, for hydrolase activitySequence Analysis
Active sitei82 – 821Nucleophile, for hydrolase activitySequence Analysis
Metal bindingi144 – 1441Manganese
Metal bindingi264 – 2641MagnesiumSequence Analysis

GO - Molecular functioni

  1. amino acid binding Source: InterPro
  2. ATP binding Source: UniProtKB-KW
  3. GTP binding Source: UniProtKB-KW
  4. GTP diphosphokinase activity Source: UniProtKB-EC
  5. guanosine-3',5'-bis(diphosphate) 3'-diphosphatase activity Source: UniProtKB-EC
  6. kinase activity Source: UniProtKB-KW
  7. metal ion binding Source: UniProtKB-KW

GO - Biological processi

  1. guanosine tetraphosphate biosynthetic process Source: UniProtKB-UniPathway
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Kinase, Transferase

Keywords - Ligandi

ATP-binding, GTP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

SABIO-RKQ54089.
UniPathwayiUPA00908; UER00884.
UPA00908; UER00886.

Names & Taxonomyi

Protein namesi
Recommended name:
Bifunctional (p)ppGpp synthase/hydrolase RelA
Including the following 2 domains:
GTP pyrophosphokinase (EC:2.7.6.5)
Alternative name(s):
(p)ppGpp synthase
ATP:GTP 3'-pyrophosphotransferase
Stringent response-like protein
ppGpp synthase I
Guanosine-3',5'-bis(diphosphate) 3'-pyrophosphohydrolase (EC:3.1.7.2)
Alternative name(s):
Penta-phosphate guanosine-3'-pyrophosphohydrolase
Short name:
(ppGpp)ase
Gene namesi
Name:relA
Synonyms:rel
OrganismiStreptococcus dysgalactiae subsp. equisimilis (Streptococcus equisimilis)
Taxonomic identifieri119602 [NCBI]
Taxonomic lineageiBacteriaFirmicutesBacilliLactobacillalesStreptococcaceaeStreptococcus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi44 – 441R → Q: No hydrolase activity. 1 Publication
Mutagenesisi78 – 781D → A: No hydrolase activity. 1 Publication
Mutagenesisi81 – 811E → G: No hydrolase activity. 1 Publication
Mutagenesisi82 – 821D → V: No hydrolase activity. 1 Publication
Mutagenesisi151 – 1511T → A or P: No hydrolase activity. 1 Publication
Mutagenesisi264 – 2641D → G: No synthase activity. 1 Publication
Mutagenesisi323 – 3231E → Q: No synthase activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 739739Bifunctional (p)ppGpp synthase/hydrolase RelAPRO_0000166565Add
BLAST

Structurei

Secondary structure

1
739
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi9 – 1911Combined sources
Helixi22 – 3817Combined sources
Turni39 – 413Combined sources
Helixi52 – 6312Combined sources
Helixi68 – 769Combined sources
Helixi79 – 824Combined sources
Helixi87 – 948Combined sources
Helixi96 – 10813Combined sources
Turni128 – 1303Combined sources
Helixi135 – 15016Combined sources
Helixi160 – 16910Combined sources
Helixi171 – 1777Combined sources
Helixi181 – 19515Combined sources
Helixi197 – 20913Combined sources
Helixi211 – 23020Combined sources
Turni231 – 2333Combined sources
Beta strandi237 – 2404Combined sources
Helixi245 – 25511Combined sources
Helixi256 – 2583Combined sources
Helixi263 – 2653Combined sources
Beta strandi267 – 2748Combined sources
Helixi275 – 28814Combined sources
Turni299 – 3013Combined sources
Beta strandi311 – 3166Combined sources
Beta strandi318 – 32811Combined sources
Helixi329 – 3379Combined sources
Helixi364 – 3707Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1VJ7X-ray2.10A/B1-385[»]
ProteinModelPortaliQ54089.
SMRiQ54089. Positions 5-371.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ54089.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini50 – 149100HDAdd
BLAST
Domaini664 – 73976ACTPROSITE-ProRule annotationAdd
BLAST

Domaini

Based on a random mutagenesis study of the catalytic fragment (residues 1-385), the (p)ppGpp phosphohydrolase domain seems to encompass approximately the first 225 residues, while the (p)ppGpp synthase domain seems to be found between residues 226 and 385.

Sequence similaritiesi

Belongs to the RelA/SpoT family.Curated
Contains 1 ACT domain.PROSITE-ProRule annotation
Contains 1 HD domain.Curated

Family and domain databases

Gene3Di3.10.20.30. 1 hit.
InterProiIPR002912. ACT_dom.
IPR012675. Beta-grasp_dom.
IPR003607. HD/PDEase_dom.
IPR006674. HD_domain.
IPR004811. RelA/Spo_fam.
IPR007685. RelA_SpoT.
IPR004095. TGS.
IPR012676. TGS-like.
[Graphical view]
PfamiPF01842. ACT. 1 hit.
PF01966. HD. 1 hit.
PF04607. RelA_SpoT. 1 hit.
PF02824. TGS. 1 hit.
[Graphical view]
SMARTiSM00471. HDc. 1 hit.
SM00954. RelA_SpoT. 1 hit.
[Graphical view]
SUPFAMiSSF81271. SSF81271. 1 hit.
TIGRFAMsiTIGR00691. spoT_relA. 1 hit.
PROSITEiPS51671. ACT. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q54089-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAKEINLTGE EVVALAAKYM NETDAAFVKK ALDYATAAHF YQVRKSGEPY
60 70 80 90 100
IVHPIQVAGI LADLHLDAVT VACGFLHDVV EDTDITLDNI EFDFGKDVRD
110 120 130 140 150
IVDGVTKLGK VEYKSHEEQL AENHRKMLMA MSKDIRVILV KLADRLHNMR
160 170 180 190 200
TLKHLRKDKQ ERISRETMEI YAPLAHRLGI SRIKWELEDL AFRYLNETEF
210 220 230 240 250
YKISHMMNEK RREREALVDD IVTKIKSYTT EQGLFGDVYG RPKHIYSIYR
260 270 280 290 300
KMRDKKKRFD QIFDLIAIRC VMETQSDVYA MVGYIHELWR PMPGRFKDYI
310 320 330 340 350
AAPKANGYQS IHTTVYGPKG PIEIQIRTKE MHQVAEYGVA AHWAYKKGVR
360 370 380 390 400
GKVNQAEQKV GMNWIKELVE LQDASNGDAV DFVDSVKEDI FSERIYVFTP
410 420 430 440 450
TGAVQELPKD SGPIDFAYAI HTQVGEKAIG AKVNGRMVPL TAKLKTGDVV
460 470 480 490 500
EIVTNPNSFG PSRDWIKLVK TNKARNKIRQ FFKNQDKELS VNKGRDMLVS
510 520 530 540 550
YFQEQGYVAN KYLDKKRIEA ILPKVSVKSE ESLYAAVGFG DISPVSVFNK
560 570 580 590 600
LTEKERREEE RAKAKAEAEE LVNGGEIKHE NKDVLKVRSE NGVIIQGASG
610 620 630 640 650
LLMRIAKCCN PVPGDPIEGY ITKGRGIAIH RADCNNIKSQ DGYQERLIEV
660 670 680 690 700
EWDLDNSSKD YQAEIDIYGL NRRGLLNDVL QILSNSTKSI STVNAQPTKD
710 720 730
MKFANIHVSF GIPNLTHLTT VVEKIKAVPD VYSVKRTNG
Length:739
Mass (Da):83,913
Last modified:November 1, 1997 - v1
Checksum:iE65CBEF99103D171
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X72832 Genomic DNA. Translation: CAA51353.1.
PIRiS39975.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X72832 Genomic DNA. Translation: CAA51353.1.
PIRiS39975.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1VJ7X-ray2.10A/B1-385[»]
ProteinModelPortaliQ54089.
SMRiQ54089. Positions 5-371.
ModBaseiSearch...
MobiDBiSearch...

Chemistry

ChEMBLiCHEMBL1163118.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Enzyme and pathway databases

UniPathwayiUPA00908; UER00884.
UPA00908; UER00886.
SABIO-RKQ54089.

Miscellaneous databases

EvolutionaryTraceiQ54089.

Family and domain databases

Gene3Di3.10.20.30. 1 hit.
InterProiIPR002912. ACT_dom.
IPR012675. Beta-grasp_dom.
IPR003607. HD/PDEase_dom.
IPR006674. HD_domain.
IPR004811. RelA/Spo_fam.
IPR007685. RelA_SpoT.
IPR004095. TGS.
IPR012676. TGS-like.
[Graphical view]
PfamiPF01842. ACT. 1 hit.
PF01966. HD. 1 hit.
PF04607. RelA_SpoT. 1 hit.
PF02824. TGS. 1 hit.
[Graphical view]
SMARTiSM00471. HDc. 1 hit.
SM00954. RelA_SpoT. 1 hit.
[Graphical view]
SUPFAMiSSF81271. SSF81271. 1 hit.
TIGRFAMsiTIGR00691. spoT_relA. 1 hit.
PROSITEiPS51671. ACT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Genetic organization of the streptokinase region of the Streptococcus equisimilis H46A chromosome."
    Mechold U., Steiner K., Vettermann S., Malke H.
    Mol. Gen. Genet. 241:129-140(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: H46A.
  2. "Intramolecular regulation of the opposing (p)ppGpp catalytic activities of Rel(Seq), the Rel/Spo enzyme from Streptococcus equisimilis."
    Mechold U., Murphy H., Brown L., Cashel M.
    J. Bacteriol. 184:2878-2888(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
  3. "Conformational antagonism between opposing active sites in a bifunctional RelA/SpoT homolog modulates (p)ppGpp metabolism during the stringent response."
    Hogg T., Mechold U., Malke H., Cashel M., Hilgenfeld R.
    Cell 117:57-68(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-385 BOUND TO GUANOSINE-NUCLEOTIDE DERIVATIVES, HYDROLASE AND SYNTHASE ACTIVITIES, COFACTOR, ENZYME REGULATION, MUTAGENESIS OF ARG-44; ASP-78; GLU-81; ASP-82; THR-151; ASP-264 AND GLU-323.
    Strain: H46A.

Entry informationi

Entry nameiRELA_STREQ
AccessioniPrimary (citable) accession number: Q54089
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: November 26, 2014
This is version 93 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.