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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

    Pathway:ippGpp biosynthesis

    This protein is involved in step 1 of the subpathway that synthesizes ppGpp from GDP.
    Proteins known to be involved in this subpathway in this organism are:
    1. Bifunctional (p)ppGpp synthase/hydrolase RelA (relA)
    This subpathway is part of the pathway ppGpp biosynthesis, which is itself part of Purine metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes ppGpp from GDP, the pathway ppGpp biosynthesis and in Purine metabolism.

    Pathway:ippGpp biosynthesis

    This protein is involved in step 1 of the subpathway that synthesizes ppGpp from GTP.
    Proteins known to be involved in the 2 steps of the subpathway in this organism are:
    1. Bifunctional (p)ppGpp synthase/hydrolase RelA (relA)
    2. no protein annotated in this organism
    This subpathway is part of the pathway ppGpp biosynthesis, which is itself part of Purine metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes ppGpp from GTP, the pathway ppGpp biosynthesis and in Purine metabolism.

    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

    GO - Biological processi

    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.